Bioinorganic Chemistry and Redox Homeostasis
Our website :
Metals in Biology and Redox Homeostasis
A new name for our research group: METROX
CONGRATULATIONS to our former PhD students:
Jean Bouvet for his selection to the MBA « collège des ingénieurs » (jan. 2024)
Paul Demay-Drouhard, who was appointed as a CNRS researcher (section 12, ICOA Orléans) in 2023
Martha Zoumpoulaki for her selection to the MBA « collège des ingénieurs » (oct. 2021) and her recruitment at Air Liquide in 2023.
Koudedja Coulibaly, who was recruited by Air Liquide in 2021
Emilie Mathieu, who was appointed as a CNRS researcher (section 16, LCC Toulouse) in 2021
Sarah Hostachy, who was appointed as a CEAEA researcher (LCBM, Grenoble) in 2020
Our personal webpages and resumes:
Alice Balfourier (ORCID: 0000-0002-4801-1388)
Hélène Bertrand (ORCID: 0000-0002-3841-022X)
Nicolas Delsuc (ORCID: 0000-0001-5570-8311)
Clotilde Policar (ORCID: 0000-0003-0255-1650)
Christine Rampon (ORCID: 0000-0002-1444-3166)
Michel Volovitch (ORCID: 0000-0002-7488-764X)
Sophie Vriz
Some news about our work:
About our work and equity in science (in French): https://www.youtube.com/watch?v=ZfyFIkh_G4k
https://www.inc.cnrs.fr/fr/cnrsinfo/des-complexes-bio-inspires-dans-le-vent
https://www.ens.psl.eu/actualites/des-catalyseurs-bio-inspires-pour-lutter-contre-le-stress-oxydant
Publications of the group:
((Go back to the publication page of the ens-bic website))
2022 |
SOD mimics: From the tool box of the chemists to cellular studies Article de journal Clotilde Policar; Jean Bouvet; Hélène C Bertrand; Nicolas Delsuc Current Opinion in Chemical Biology, 67 , p. 102109, 2022, ISSN: 1367-5931. @article{POLICAR2022102109, title = {SOD mimics: From the tool box of the chemists to cellular studies}, author = {Clotilde Policar and Jean Bouvet and H\'{e}l\`{e}ne C Bertrand and Nicolas Delsuc}, url = {https://www.sciencedirect.com/science/article/pii/S136759312100154X}, doi = {https://doi.org/10.1016/j.cbpa.2021.102109}, issn = {1367-5931}, year = {2022}, date = {2022-01-01}, journal = {Current Opinion in Chemical Biology}, volume = {67}, pages = {102109}, abstract = {Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2−) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2−) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments. |
Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives Article de journal Alexander I Kostyuk; Maria-Armineh Tossounian; Anastasiya S Panova; Marion Thauvin; Roman I Raevskii; Daria Ezeriņa; Khadija Wahni; Inge Van Molle; Anastasia D Sergeeva; Didier Vertommen; Andrey Yu. Gorokhovatsky; Mikhail S Baranov; Sophie Vriz; Joris Messens; Dmitry S Bilan; Vsevolod V Belousov Nature Communications, 13 , p. 171, 2022, ISSN: 2041-1723. @article{kostyuk_hypocrates_2022, title = {Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives}, author = {Alexander I Kostyuk and Maria-Armineh Tossounian and Anastasiya S Panova and Marion Thauvin and Roman I Raevskii and Daria Ezeri\c{n}a and Khadija Wahni and Inge Van Molle and Anastasia D Sergeeva and Didier Vertommen and Andrey Yu. Gorokhovatsky and Mikhail S Baranov and Sophie Vriz and Joris Messens and Dmitry S Bilan and Vsevolod V Belousov}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748444/}, doi = {10.1038/s41467-021-27796-2}, issn = {2041-1723}, year = {2022}, date = {2022-01-01}, urldate = {2023-10-31}, journal = {Nature Communications}, volume = {13}, pages = {171}, abstract = {The lack of tools to monitor the dynamics of (pseudo)hypohalous acids in live cells and tissues hinders a better understanding of inflammatory processes. Here we present a fluorescent genetically encoded biosensor, Hypocrates, for the visualization of (pseudo)hypohalous acids and their derivatives. Hypocrates consists of a circularly permuted yellow fluorescent protein integrated into the structure of the transcription repressor NemR from Escherichia coli. We show that Hypocrates is ratiometric, reversible, and responds to its analytes in the 106 M−1s−1 range. Solving the Hypocrates X-ray structure provided insights into its sensing mechanism, allowing determination of the spatial organization in this circularly permuted fluorescent protein-based redox probe. We exemplify its applicability by imaging hypohalous stress in bacteria phagocytosed by primary neutrophils. Finally, we demonstrate that Hypocrates can be utilized in combination with HyPerRed for the simultaneous visualization of (pseudo)hypohalous acids and hydrogen peroxide dynamics in a zebrafish tail fin injury model., There are a lack of tools to study the dynamics of (pseudo)hypohalous acids in live cells. Here the authors report a genetically encoded fluorescent biosensor, Hypocrates, for (pseudo)hypohalous acids and their derivatives which they use in cells and in a zebrafish tail fin injury model.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The lack of tools to monitor the dynamics of (pseudo)hypohalous acids in live cells and tissues hinders a better understanding of inflammatory processes. Here we present a fluorescent genetically encoded biosensor, Hypocrates, for the visualization of (pseudo)hypohalous acids and their derivatives. Hypocrates consists of a circularly permuted yellow fluorescent protein integrated into the structure of the transcription repressor NemR from Escherichia coli. We show that Hypocrates is ratiometric, reversible, and responds to its analytes in the 106 M−1s−1 range. Solving the Hypocrates X-ray structure provided insights into its sensing mechanism, allowing determination of the spatial organization in this circularly permuted fluorescent protein-based redox probe. We exemplify its applicability by imaging hypohalous stress in bacteria phagocytosed by primary neutrophils. Finally, we demonstrate that Hypocrates can be utilized in combination with HyPerRed for the simultaneous visualization of (pseudo)hypohalous acids and hydrogen peroxide dynamics in a zebrafish tail fin injury model., There are a lack of tools to study the dynamics of (pseudo)hypohalous acids in live cells. Here the authors report a genetically encoded fluorescent biosensor, Hypocrates, for (pseudo)hypohalous acids and their derivatives which they use in cells and in a zebrafish tail fin injury model. |
Fgf8 dynamics and critical slowing down may account for the temperature independence of somitogenesis Article de journal Weiting Zhang; Pierluigi Scerbo; Marine Delagrange; Virginie Candat; Vanessa Mayr; Sophie Vriz; Martin Distel; Bertrand Ducos; David Bensimon Communications Biology, 5 (1), p. 1–10, 2022, ISSN: 2399-3642, (Number: 1 Publisher: Nature Publishing Group). @article{zhang_fgf8_2022, title = {Fgf8 dynamics and critical slowing down may account for the temperature independence of somitogenesis}, author = {Weiting Zhang and Pierluigi Scerbo and Marine Delagrange and Virginie Candat and Vanessa Mayr and Sophie Vriz and Martin Distel and Bertrand Ducos and David Bensimon}, url = {https://www.nature.com/articles/s42003-022-03053-0}, doi = {10.1038/s42003-022-03053-0}, issn = {2399-3642}, year = {2022}, date = {2022-01-01}, urldate = {2023-10-31}, journal = {Communications Biology}, volume = {5}, number = {1}, pages = {1--10}, abstract = {Somitogenesis, the segmentation of the antero-posterior axis in vertebrates, is thought to result from the interactions between a genetic oscillator and a posterior-moving determination wavefront. The segment (somite) size is set by the product of the oscillator period and the velocity of the determination wavefront. Surprisingly, while the segmentation period can vary by a factor three between 20 °C and 32 °C, the somite size is constant. How this temperature independence is achieved is a mystery that we address in this study. Using RT-qPCR we show that the endogenous fgf8 mRNA concentration decreases during somitogenesis and correlates with the exponent of the shrinking pre-somitic mesoderm (PSM) size. As the temperature decreases, the dynamics of fgf8 and many other gene transcripts, as well as the segmentation frequency and the PSM shortening and tail growth rates slows down as T\textendashTc (with Tc = 14.4 °C). This behavior characteristic of a system near a critical point may account for the temperature independence of somitogenesis in zebrafish.}, note = {Number: 1 Publisher: Nature Publishing Group}, keywords = {}, pubstate = {published}, tppubtype = {article} } Somitogenesis, the segmentation of the antero-posterior axis in vertebrates, is thought to result from the interactions between a genetic oscillator and a posterior-moving determination wavefront. The segment (somite) size is set by the product of the oscillator period and the velocity of the determination wavefront. Surprisingly, while the segmentation period can vary by a factor three between 20 °C and 32 °C, the somite size is constant. How this temperature independence is achieved is a mystery that we address in this study. Using RT-qPCR we show that the endogenous fgf8 mRNA concentration decreases during somitogenesis and correlates with the exponent of the shrinking pre-somitic mesoderm (PSM) size. As the temperature decreases, the dynamics of fgf8 and many other gene transcripts, as well as the segmentation frequency and the PSM shortening and tail growth rates slows down as T–Tc (with Tc = 14.4 °C). This behavior characteristic of a system near a critical point may account for the temperature independence of somitogenesis in zebrafish. |
Reciprocal Regulation of Shh Trafficking and H2O2 Levels via a Noncanonical BOC-Rac1 Pathway Article de journal Marion Thauvin; Irène Amblard; Christine Rampon; Aurélien Mourton; Isabelle Queguiner; Chenge Li; Arnaud Gautier; Alain Joliot; Michel Volovitch; Sophie Vriz Antioxidants (Basel, Switzerland), 11 (4), p. 718, 2022, ISSN: 2076-3921. @article{thauvin_reciprocal_2022, title = {Reciprocal Regulation of Shh Trafficking and H2O2 Levels via a Noncanonical BOC-Rac1 Pathway}, author = {Marion Thauvin and Ir\`{e}ne Amblard and Christine Rampon and Aur\'{e}lien Mourton and Isabelle Queguiner and Chenge Li and Arnaud Gautier and Alain Joliot and Michel Volovitch and Sophie Vriz}, doi = {10.3390/antiox11040718}, issn = {2076-3921}, year = {2022}, date = {2022-01-01}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {718}, abstract = {Among molecules that bridge environment, cell metabolism, and cell signaling, hydrogen peroxide (H2O2) recently appeared as an emerging but central player. Its level depends on cell metabolism and environment and was recently shown to play key roles during embryogenesis, contrasting with its long-established role in disease progression. We decided to explore whether the secreted morphogen Sonic hedgehog (Shh), known to be essential in a variety of biological processes ranging from embryonic development to adult tissue homeostasis and cancers, was part of these interactions. Here, we report that H2O2 levels control key steps of Shh delivery in cell culture: increased levels reduce primary secretion, stimulate endocytosis and accelerate delivery to recipient cells; in addition, physiological in vivo modulation of H2O2 levels changes Shh distribution and tissue patterning. Moreover, a feedback loop exists in which Shh trafficking controls H2O2 synthesis via a non-canonical BOC-Rac1 pathway, leading to cytoneme growth. Our findings reveal that Shh directly impacts its own distribution, thus providing a molecular explanation for the robustness of morphogenesis to both environmental insults and individual variability.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Among molecules that bridge environment, cell metabolism, and cell signaling, hydrogen peroxide (H2O2) recently appeared as an emerging but central player. Its level depends on cell metabolism and environment and was recently shown to play key roles during embryogenesis, contrasting with its long-established role in disease progression. We decided to explore whether the secreted morphogen Sonic hedgehog (Shh), known to be essential in a variety of biological processes ranging from embryonic development to adult tissue homeostasis and cancers, was part of these interactions. Here, we report that H2O2 levels control key steps of Shh delivery in cell culture: increased levels reduce primary secretion, stimulate endocytosis and accelerate delivery to recipient cells; in addition, physiological in vivo modulation of H2O2 levels changes Shh distribution and tissue patterning. Moreover, a feedback loop exists in which Shh trafficking controls H2O2 synthesis via a non-canonical BOC-Rac1 pathway, leading to cytoneme growth. Our findings reveal that Shh directly impacts its own distribution, thus providing a molecular explanation for the robustness of morphogenesis to both environmental insults and individual variability. |
NADPH-Oxidase Derived Hydrogen Peroxide and Irs2b Facilitate Re-oxygenation-Induced Catch-Up Growth in Zebrafish Embryo Article de journal Ayaka Zasu; Futa Hishima; Marion Thauvin; Yosuke Yoneyama; Yoichiro Kitani; Fumihiko Hakuno; Michel Volovitch; Shin-Ichiro Takahashi; Sophie Vriz; Christine Rampon; Hiroyasu Kamei Frontiers in Endocrinology, 13 , 2022, ISSN: 1664-2392. @article{zasu_nadph-oxidase_2022, title = {NADPH-Oxidase Derived Hydrogen Peroxide and Irs2b Facilitate Re-oxygenation-Induced Catch-Up Growth in Zebrafish Embryo}, author = {Ayaka Zasu and Futa Hishima and Marion Thauvin and Yosuke Yoneyama and Yoichiro Kitani and Fumihiko Hakuno and Michel Volovitch and Shin-Ichiro Takahashi and Sophie Vriz and Christine Rampon and Hiroyasu Kamei}, url = {https://www.frontiersin.org/articles/10.3389/fendo.2022.929668}, issn = {1664-2392}, year = {2022}, date = {2022-01-01}, urldate = {2023-10-31}, journal = {Frontiers in Endocrinology}, volume = {13}, abstract = {Oxygen deprivation induces multiple changes at the cellular and organismal levels, and its re-supply also brings another special physiological status. We have investigated the effects of hypoxia/re-oxygenation on embryonic growth using the zebrafish model: hypoxia slows embryonic growth, but re-oxygenation induces growth spurt or catch-up growth. The mitogen-activated kinase (MAPK)-pathway downstream insulin-like growth factor (IGF/Igf) has been revealed to positively regulate the re-oxygenation-induced catch-up growth, and the role of reactive oxygen species generated by environmental oxygen fluctuation is potentially involved in the phenomenon. Here, we report the role of NADPH-oxidase (Nox)-dependent hydrogen peroxide (H2O2) production in the MAPK-activation and catch-up growth. The inhibition of Nox significantly blunted catch-up growth and MAPK-activity. Amongst two zebrafish insulin receptor substrate 2 genes (irs2a and irs2b), the loss of irs2b, but not its paralog irs2a, resulted in blunted MAPK-activation and catch-up growth. Furthermore, irs2b forcedly expressed in mammalian cells allowed IGF-MAPK augmentation in the presence of H2O2, and the irs2b deficiency completely abolished the somatotropic action of Nox in re-oxygenation condition. These results indicate that redox signaling alters IGF/Igf signaling to facilitate hypoxia/re-oxygenation-induced embryonic growth compensation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxygen deprivation induces multiple changes at the cellular and organismal levels, and its re-supply also brings another special physiological status. We have investigated the effects of hypoxia/re-oxygenation on embryonic growth using the zebrafish model: hypoxia slows embryonic growth, but re-oxygenation induces growth spurt or catch-up growth. The mitogen-activated kinase (MAPK)-pathway downstream insulin-like growth factor (IGF/Igf) has been revealed to positively regulate the re-oxygenation-induced catch-up growth, and the role of reactive oxygen species generated by environmental oxygen fluctuation is potentially involved in the phenomenon. Here, we report the role of NADPH-oxidase (Nox)-dependent hydrogen peroxide (H2O2) production in the MAPK-activation and catch-up growth. The inhibition of Nox significantly blunted catch-up growth and MAPK-activity. Amongst two zebrafish insulin receptor substrate 2 genes (irs2a and irs2b), the loss of irs2b, but not its paralog irs2a, resulted in blunted MAPK-activation and catch-up growth. Furthermore, irs2b forcedly expressed in mammalian cells allowed IGF-MAPK augmentation in the presence of H2O2, and the irs2b deficiency completely abolished the somatotropic action of Nox in re-oxygenation condition. These results indicate that redox signaling alters IGF/Igf signaling to facilitate hypoxia/re-oxygenation-induced embryonic growth compensation. |
An early Shh-H2O2 reciprocal regulatory interaction controls the regenerative program during zebrafish fin regeneration Article de journal Marion Thauvin; Rodolphe Matias de Sousa; Marine Alves; Michel Volovitch; Sophie Vriz; Christine Rampon Journal of Cell Science, 135 (6), p. jcs259664, 2022, ISSN: 1477-9137. @article{thauvin_early_2022, title = {An early Shh-H2O2 reciprocal regulatory interaction controls the regenerative program during zebrafish fin regeneration}, author = {Marion Thauvin and Rodolphe Matias de Sousa and Marine Alves and Michel Volovitch and Sophie Vriz and Christine Rampon}, doi = {10.1242/jcs.259664}, issn = {1477-9137}, year = {2022}, date = {2022-01-01}, journal = {Journal of Cell Science}, volume = {135}, number = {6}, pages = {jcs259664}, abstract = {Reactive oxygen species (ROS), originally classified as toxic molecules, have attracted increasing interest given their actions in cell signaling. Hydrogen peroxide (H2O2), the major ROS produced by cells, acts as a second messenger to modify redox-sensitive proteins or lipids. After caudal fin amputation, tight spatiotemporal regulation of ROS is required first for wound healing and later to initiate the regenerative program. However, the mechanisms carrying out this sustained ROS production and their integration with signaling pathways remain poorly understood. We focused on the early dialog between H2O2 and Sonic hedgehog (Shh) during zebrafish fin regeneration. We demonstrate that H2O2 controls Shh expression and that Shh in turn regulates the H2O2 level via a canonical pathway. Moreover, the means of this tight reciprocal control change during the successive phases of the regenerative program. Dysregulation of the Hedgehog pathway has been implicated in several developmental syndromes, diabetes and cancer. These data support the existence of an early positive crosstalk between Shh and H2O2 that might be more generally involved in various processes paving the way to improve regenerative processes, particularly in vertebrates.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Reactive oxygen species (ROS), originally classified as toxic molecules, have attracted increasing interest given their actions in cell signaling. Hydrogen peroxide (H2O2), the major ROS produced by cells, acts as a second messenger to modify redox-sensitive proteins or lipids. After caudal fin amputation, tight spatiotemporal regulation of ROS is required first for wound healing and later to initiate the regenerative program. However, the mechanisms carrying out this sustained ROS production and their integration with signaling pathways remain poorly understood. We focused on the early dialog between H2O2 and Sonic hedgehog (Shh) during zebrafish fin regeneration. We demonstrate that H2O2 controls Shh expression and that Shh in turn regulates the H2O2 level via a canonical pathway. Moreover, the means of this tight reciprocal control change during the successive phases of the regenerative program. Dysregulation of the Hedgehog pathway has been implicated in several developmental syndromes, diabetes and cancer. These data support the existence of an early positive crosstalk between Shh and H2O2 that might be more generally involved in various processes paving the way to improve regenerative processes, particularly in vertebrates. |
2021 |
Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil–Gold Nanoparticle Complexes Article de journal Vladimir Mulens-Arias; Alba Nicolás-Boluda; Amandine Pinto; Alice Balfourier; Florent Carn; Amanda K A Silva; Marc Pocard; Florence Gazeau ACS Nano, 15 (2), p. 3330–3348, 2021, ISSN: 1936-0851, 1936-086X. @article{mulens-arias_tumor-selective_2021, title = {Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil\textendashGold Nanoparticle Complexes}, author = {Vladimir Mulens-Arias and Alba Nicol\'{a}s-Boluda and Amandine Pinto and Alice Balfourier and Florent Carn and Amanda K A Silva and Marc Pocard and Florence Gazeau}, url = {https://pubs.acs.org/doi/10.1021/acsnano.0c10276}, doi = {10.1021/acsnano.0c10276}, issn = {1936-0851, 1936-086X}, year = {2021}, date = {2021-02-01}, urldate = {2022-04-29}, journal = {ACS Nano}, volume = {15}, number = {2}, pages = {3330--3348}, abstract = {Peritoneal metastasis (PM) is considered as the terminal stage of metastatic colon cancer, with still poor median survival rate even with the best recent chemotherapy treatment. The current PM treatment combines cytoreductive surgery, which consists of resecting all macroscopic tumors, with hyperthermic intraperitoneal chemotherapy (HIPEC), which uses mild hyperthermia to boost the diffusion and cytotoxic effect of chemotherapeutic drugs. As HIPEC is performed via a closed circulation of a hot liquid containing chemotherapy, it induces uncontrolled heating and drug distribution in the whole peritoneal cavity with important off-site toxicity and a high level of morbidity. Here, we propose a safer precision strategy using near-infrared (NIR) photoactivated gold nanoparticles (AuNPs) coupled to the chemotherapeutic drug 5-fluorouracil (5-FU) to enable a spatial and temporal control of mild chemo-hyperthermia targeted to the tumor nodules within the peritoneal cavity. Both the 16 nm AuNPs and the corresponding complex with 5-FU (AuNP−5-FU) were shown as efficient NIR photothermal agents in the microenvironment of subcutaneous colon tumors as well as PM in syngeneic mice. Noteworthy, NIR photothermia provided additional antitumor effects to 5-FU treatment. A single intraperitoneal administration of AuNP−5-FU resulted in their preferential accumulation in tumor nodules and peritoneal macrophages, allowing light-induced selective hyperthermia, extended tumor necrosis, and activation of a pro-inflammatory immune response while leaving healthy tissues without any damage. From a translational standpoint, the combined and tumor-targeted photothermal and chemotherapy mediated by the AuNP−drug complex has the potential to overcome the current off-target toxicity of HIPEC in clinical practice.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Peritoneal metastasis (PM) is considered as the terminal stage of metastatic colon cancer, with still poor median survival rate even with the best recent chemotherapy treatment. The current PM treatment combines cytoreductive surgery, which consists of resecting all macroscopic tumors, with hyperthermic intraperitoneal chemotherapy (HIPEC), which uses mild hyperthermia to boost the diffusion and cytotoxic effect of chemotherapeutic drugs. As HIPEC is performed via a closed circulation of a hot liquid containing chemotherapy, it induces uncontrolled heating and drug distribution in the whole peritoneal cavity with important off-site toxicity and a high level of morbidity. Here, we propose a safer precision strategy using near-infrared (NIR) photoactivated gold nanoparticles (AuNPs) coupled to the chemotherapeutic drug 5-fluorouracil (5-FU) to enable a spatial and temporal control of mild chemo-hyperthermia targeted to the tumor nodules within the peritoneal cavity. Both the 16 nm AuNPs and the corresponding complex with 5-FU (AuNP−5-FU) were shown as efficient NIR photothermal agents in the microenvironment of subcutaneous colon tumors as well as PM in syngeneic mice. Noteworthy, NIR photothermia provided additional antitumor effects to 5-FU treatment. A single intraperitoneal administration of AuNP−5-FU resulted in their preferential accumulation in tumor nodules and peritoneal macrophages, allowing light-induced selective hyperthermia, extended tumor necrosis, and activation of a pro-inflammatory immune response while leaving healthy tissues without any damage. From a translational standpoint, the combined and tumor-targeted photothermal and chemotherapy mediated by the AuNP−drug complex has the potential to overcome the current off-target toxicity of HIPEC in clinical practice. |
Rhenium carbonyl complexes bearing methylated triphenylphosphonium cations as antibody-free mitochondria trackers for X-ray fluorescence imaging Article de journal Gabrielle Schanne; Lucas Henry; How Chee Ong; Andrea Somogyi; Kadda Medjoubi; Nicolas Delsuc; Clotilde Policar; Felipe García; Helene C Bertrand Inorg. Chem. Front., 8 , p. 3905-3915, 2021. @article{D1QI00542A, title = {Rhenium carbonyl complexes bearing methylated triphenylphosphonium cations as antibody-free mitochondria trackers for X-ray fluorescence imaging}, author = {Gabrielle Schanne and Lucas Henry and How Chee Ong and Andrea Somogyi and Kadda Medjoubi and Nicolas Delsuc and Clotilde Policar and Felipe Garc\'{i}a and Helene C Bertrand}, url = {http://dx.doi.org/10.1039/D1QI00542A}, doi = {10.1039/D1QI00542A}, year = {2021}, date = {2021-01-01}, journal = {Inorg. Chem. Front.}, volume = {8}, pages = {3905-3915}, publisher = {The Royal Society of Chemistry}, abstract = {Synchrotron Radiation X-ray Fluorescence (SXRF) imaging is a powerful technique for the visualization of metal complexes in biological systems. However, due to the lack of an endogenous elemental signature for mitochondria, probes for the localization of this organelle are required for colocalization studies. In this work, we designed and synthesized rhenium pyta tricarbonyl complexes conjugated to methylated triphenylphosphonium TP*P+ cations as multimodal probes for the visualization of mitochondria, suitable for fluorescence and SXRF imaging and quantification. Accumulation of the methylated triphenylphosphonium TP*P+-based conjugates in cells was observed in fixed A549 cells, and the amount of mitochondrial uptake was linked to the lipophilicity of the TPP+ vector. Our work highlights a convenient rhenium-based multimodal mitochondrial-targeted probe compatible with SXRF nano-imaging.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Synchrotron Radiation X-ray Fluorescence (SXRF) imaging is a powerful technique for the visualization of metal complexes in biological systems. However, due to the lack of an endogenous elemental signature for mitochondria, probes for the localization of this organelle are required for colocalization studies. In this work, we designed and synthesized rhenium pyta tricarbonyl complexes conjugated to methylated triphenylphosphonium TP*P+ cations as multimodal probes for the visualization of mitochondria, suitable for fluorescence and SXRF imaging and quantification. Accumulation of the methylated triphenylphosphonium TP*P+-based conjugates in cells was observed in fixed A549 cells, and the amount of mitochondrial uptake was linked to the lipophilicity of the TPP+ vector. Our work highlights a convenient rhenium-based multimodal mitochondrial-targeted probe compatible with SXRF nano-imaging. |
Orthogonal fluorescent chemogenetic reporters for multicolor imaging Article de journal Alison G Tebo; Benjamien Moeyaert; Marion Thauvin; Irene Carlon-Andres; Dorothea Böken; Michel Volovitch; Sergi Padilla-Parra; Peter Dedecker; Sophie Vriz; Arnaud Gautier Nature Chemical Biology, 17 (1), p. 30–38, 2021, ISSN: 1552-4469. @article{tebo_orthogonal_2021, title = {Orthogonal fluorescent chemogenetic reporters for multicolor imaging}, author = {Alison G Tebo and Benjamien Moeyaert and Marion Thauvin and Irene Carlon-Andres and Dorothea B\"{o}ken and Michel Volovitch and Sergi Padilla-Parra and Peter Dedecker and Sophie Vriz and Arnaud Gautier}, doi = {10.1038/s41589-020-0611-0}, issn = {1552-4469}, year = {2021}, date = {2021-01-01}, journal = {Nature Chemical Biology}, volume = {17}, number = {1}, pages = {30--38}, abstract = {Spectrally separated fluorophores allow the observation of multiple targets simultaneously inside living cells, leading to a deeper understanding of the molecular interplay that regulates cell function and fate. Chemogenetic systems combining a tag and a synthetic fluorophore provide certain advantages over fluorescent proteins since there is no requirement for chromophore maturation. Here, we present the engineering of a set of spectrally orthogonal fluorogen-activating tags based on the fluorescence-activating and absorption shifting tag (FAST) that are compatible with two-color, live-cell imaging. The resulting tags, greenFAST and redFAST, demonstrate orthogonality not only in their fluorogen recognition capabilities, but also in their one- and two-photon absorption profiles. This pair of orthogonal tags allowed the creation of a two-color cell cycle sensor capable of detecting very short, early cell cycles in zebrafish development and the development of split complementation systems capable of detecting multiple protein-protein interactions by live-cell fluorescence microscopy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Spectrally separated fluorophores allow the observation of multiple targets simultaneously inside living cells, leading to a deeper understanding of the molecular interplay that regulates cell function and fate. Chemogenetic systems combining a tag and a synthetic fluorophore provide certain advantages over fluorescent proteins since there is no requirement for chromophore maturation. Here, we present the engineering of a set of spectrally orthogonal fluorogen-activating tags based on the fluorescence-activating and absorption shifting tag (FAST) that are compatible with two-color, live-cell imaging. The resulting tags, greenFAST and redFAST, demonstrate orthogonality not only in their fluorogen recognition capabilities, but also in their one- and two-photon absorption profiles. This pair of orthogonal tags allowed the creation of a two-color cell cycle sensor capable of detecting very short, early cell cycles in zebrafish development and the development of split complementation systems capable of detecting multiple protein-protein interactions by live-cell fluorescence microscopy. |
Arnaud Gautier; Ludovic Jullien; Chenge Li; Marie-Aude Plamont; Alison G Tebo; Marion Thauvin; Michel Volovitch; Sophie Vriz Springer US, New York, NY, 2021, ISBN: 978-1-07-161593-5. @book{gautier_versatile_2021, title = {Versatile On-Demand Fluorescent Labeling of Fusion Proteins Using Fluorescence-Activating and Absorption-Shifting Tag (FAST)}, author = {Arnaud Gautier and Ludovic Jullien and Chenge Li and Marie-Aude Plamont and Alison G Tebo and Marion Thauvin and Michel Volovitch and Sophie Vriz}, editor = {Eli Zamir}, url = {https://doi.org/10.1007/978-1-0716-1593-5_16}, doi = {10.1007/978-1-0716-1593-5_16}, isbn = {978-1-07-161593-5}, year = {2021}, date = {2021-01-01}, urldate = {2023-10-31}, booktitle = {Multiplexed Imaging: Methods and Protocols}, pages = {253--265}, publisher = {Springer US}, address = {New York, NY}, series = {Methods in Molecular Biology}, abstract = {Observing the localization, the concentration, and the distribution of proteins in cells or organisms is essential to understand theirs functions. General and versatile methods allowing multiplexed imaging of proteins under a large variety of experimental conditions are thus essential for deciphering the inner workings of cells and organisms. Here, we present a general method based on the non-covalent labeling of a small protein tag, named FAST (fluorescence-activating and absorption-shifting tag), with various fluorogenic ligands that light up upon labeling, which makes the simple, robust, and versatile on-demand labeling of fusion proteins in a wide range of experimental systems possible.}, keywords = {}, pubstate = {published}, tppubtype = {book} } Observing the localization, the concentration, and the distribution of proteins in cells or organisms is essential to understand theirs functions. General and versatile methods allowing multiplexed imaging of proteins under a large variety of experimental conditions are thus essential for deciphering the inner workings of cells and organisms. Here, we present a general method based on the non-covalent labeling of a small protein tag, named FAST (fluorescence-activating and absorption-shifting tag), with various fluorogenic ligands that light up upon labeling, which makes the simple, robust, and versatile on-demand labeling of fusion proteins in a wide range of experimental systems possible. |
Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models Article de journal Amandine Vincent; Marion Thauvin; Elodie Quévrain; Emilie Mathieu; Sarah Layani; Philippe Seksik; Ines Batinic-Haberle; Sophie Vriz; Clotilde Policar; Nicolas Delsuc Journal of Inorganic Biochemistry, p. 111431, 2021, ISSN: 0162-0134. @article{VINCENT2021111431, title = {Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models}, author = {Amandine Vincent and Marion Thauvin and Elodie Qu\'{e}vrain and Emilie Mathieu and Sarah Layani and Philippe Seksik and Ines Batinic-Haberle and Sophie Vriz and Clotilde Policar and Nicolas Delsuc}, url = {https://www.sciencedirect.com/science/article/pii/S0162013421000787}, doi = {https://doi.org/10.1016/j.jinorgbio.2021.111431}, issn = {0162-0134}, year = {2021}, date = {2021-01-01}, journal = {Journal of Inorganic Biochemistry}, pages = {111431}, abstract = {Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2′-nbutoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5, 6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1, 4, 7, 10] tetra--azacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N′-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2′-nbutoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5, 6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1, 4, 7, 10] tetra--azacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N′-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels. |
A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme Article de journal Koudedja Coulibaly; Marion Thauvin; Adyn Melenbacher; Clara Testard; Evangelina Trigoni; Amandine Vincent; Martin J Stillman; Sophie Vriz; Clotilde Policar; Nicolas Delsuc Inorganic Chemistry, 60 (13), p. 9309-9319, 2021. @article{doi:10.1021/acs.inorgchem.0c03718b, title = {A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme}, author = {Koudedja Coulibaly and Marion Thauvin and Adyn Melenbacher and Clara Testard and Evangelina Trigoni and Amandine Vincent and Martin J Stillman and Sophie Vriz and Clotilde Policar and Nicolas Delsuc}, url = {https://doi.org/10.1021/acs.inorgchem.0c03718}, doi = {10.1021/acs.inorgchem.0c03718}, year = {2021}, date = {2021-01-01}, journal = {Inorganic Chemistry}, volume = {60}, number = {13}, pages = {9309-9319}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
2020 |
Extracellular Pax6 Regulates Tangential Cajal–Retzius Cell Migration in the Developing Mouse Neocortex Article de journal H Kaddour; E Coppola; A A Di Nardo; C Le Poupon; P Mailly; A Wizenmann; M Volovitch; A Prochiantz; A Pierani Cerebral Cortex, 30 (2), p. 465–475, 2020, ISSN: 1047-3211. @article{kaddour_extracellular_2020, title = {Extracellular Pax6 Regulates Tangential Cajal\textendashRetzius Cell Migration in the Developing Mouse Neocortex}, author = {H Kaddour and E Coppola and A A Di Nardo and C Le Poupon and P Mailly and A Wizenmann and M Volovitch and A Prochiantz and A Pierani}, url = {https://doi.org/10.1093/cercor/bhz098}, doi = {10.1093/cercor/bhz098}, issn = {1047-3211}, year = {2020}, date = {2020-01-01}, urldate = {2023-10-31}, journal = {Cerebral Cortex}, volume = {30}, number = {2}, pages = {465--475}, abstract = {The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal\textendashRetzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal–Retzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development. |
Unexpected intracellular biodegradation and recrystallization of gold nanoparticles Article de journal Alice Balfourier; Nathalie Luciani; Guillaume Wang; Gerald Lelong; Ovidiu Ersen; Abdelali Khelfa; Damien Alloyeau; Florence Gazeau; Florent Carn Proceedings of the National Academy of Sciences, 117 (1), p. 103–113, 2020, ISSN: 0027-8424, 1091-6490. @article{balfourier_unexpected_2020, title = {Unexpected intracellular biodegradation and recrystallization of gold nanoparticles}, author = {Alice Balfourier and Nathalie Luciani and Guillaume Wang and Gerald Lelong and Ovidiu Ersen and Abdelali Khelfa and Damien Alloyeau and Florence Gazeau and Florent Carn}, url = {https://pnas.org/doi/full/10.1073/pnas.1911734116}, doi = {10.1073/pnas.1911734116}, issn = {0027-8424, 1091-6490}, year = {2020}, date = {2020-01-01}, urldate = {2022-03-30}, journal = {Proceedings of the National Academy of Sciences}, volume = {117}, number = {1}, pages = {103--113}, abstract = {Significance While gold nanoparticles are at the core of an increasing range of medical applications, their fate in the organism has barely been studied so far. Because of their chemical inertness, common belief is that gold nanoparticles remain endlessly intact in tissues. We show that 4- to 22-nm gold nanoparticles are actually degraded in vitro by cells, with a faster degradation of the smallest size. Transcriptomics studies reveal the active role of cell lysosome into this biodissolution. Furthermore, we point out that the released gold recrystallizes into biopersistent nanostructures. Interestingly, these degradation products are similar to previously observed gold deposits in human tissues after gold salts treatment for rheumatoid arthritis, underlying a common metabolism between gold nanoparticles and ionic gold. , Gold nanoparticles are used in an expanding spectrum of biomedical applications. However, little is known about their long-term fate in the organism as it is generally admitted that the inertness of gold nanoparticles prevents their biodegradation. In this work, the biotransformations of gold nanoparticles captured by primary fibroblasts were monitored during up to 6 mo. The combination of electron microscopy imaging and transcriptomics study reveals an unexpected 2-step process of biotransformation. First, there is the degradation of gold nanoparticles, with faster disappearance of the smallest size. This degradation is mediated by NADPH oxidase that produces highly oxidizing reactive oxygen species in the lysosome combined with a cell-protective expression of the nuclear factor, erythroid 2. Second, a gold recrystallization process generates biomineralized nanostructures consisting of 2.5-nm crystalline particles self-assembled into nanoleaves. Metallothioneins are strongly suspected to participate in buildings blocks biomineralization that self-assembles in a process that could be affected by a chelating agent. These degradation products are similar to aurosomes structures revealed 50 y ago in vivo after gold salt therapy. Overall, we bring to light steps in the lifecycle of gold nanoparticles in which cellular pathways are partially shared with ionic gold, revealing a common gold metabolism.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Significance While gold nanoparticles are at the core of an increasing range of medical applications, their fate in the organism has barely been studied so far. Because of their chemical inertness, common belief is that gold nanoparticles remain endlessly intact in tissues. We show that 4- to 22-nm gold nanoparticles are actually degraded in vitro by cells, with a faster degradation of the smallest size. Transcriptomics studies reveal the active role of cell lysosome into this biodissolution. Furthermore, we point out that the released gold recrystallizes into biopersistent nanostructures. Interestingly, these degradation products are similar to previously observed gold deposits in human tissues after gold salts treatment for rheumatoid arthritis, underlying a common metabolism between gold nanoparticles and ionic gold. , Gold nanoparticles are used in an expanding spectrum of biomedical applications. However, little is known about their long-term fate in the organism as it is generally admitted that the inertness of gold nanoparticles prevents their biodegradation. In this work, the biotransformations of gold nanoparticles captured by primary fibroblasts were monitored during up to 6 mo. The combination of electron microscopy imaging and transcriptomics study reveals an unexpected 2-step process of biotransformation. First, there is the degradation of gold nanoparticles, with faster disappearance of the smallest size. This degradation is mediated by NADPH oxidase that produces highly oxidizing reactive oxygen species in the lysosome combined with a cell-protective expression of the nuclear factor, erythroid 2. Second, a gold recrystallization process generates biomineralized nanostructures consisting of 2.5-nm crystalline particles self-assembled into nanoleaves. Metallothioneins are strongly suspected to participate in buildings blocks biomineralization that self-assembles in a process that could be affected by a chelating agent. These degradation products are similar to aurosomes structures revealed 50 y ago in vivo after gold salt therapy. Overall, we bring to light steps in the lifecycle of gold nanoparticles in which cellular pathways are partially shared with ionic gold, revealing a common gold metabolism. |
Gold-based therapy: From past to present Article de journal Alice Balfourier; Jelena Kolosnjaj-Tabi; Nathalie Luciani; Florent Carn; Florence Gazeau Proceedings of the National Academy of Sciences, 117 (37), p. 22639–22648, 2020, (Publisher: Proceedings of the National Academy of Sciences). @article{balfourier_gold-based_2020, title = {Gold-based therapy: From past to present}, author = {Alice Balfourier and Jelena Kolosnjaj-Tabi and Nathalie Luciani and Florent Carn and Florence Gazeau}, url = {https://www.pnas.org/doi/abs/10.1073/pnas.2007285117}, doi = {10.1073/pnas.2007285117}, year = {2020}, date = {2020-01-01}, urldate = {2022-03-30}, journal = {Proceedings of the National Academy of Sciences}, volume = {117}, number = {37}, pages = {22639--22648}, note = {Publisher: Proceedings of the National Academy of Sciences}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
H2O2 and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum Article de journal Irène Amblard; Marion Thauvin; Christine Rampon; Isabelle Queguiner; Valeriy V Pak; Vsevolod Belousov; Alain Prochiantz; Michel Volovitch; Alain Joliot; Sophie Vriz Communications Biology, 3 (1), p. 1–9, 2020, ISSN: 2399-3642, (Number: 1 Publisher: Nature Publishing Group). @article{amblard_h2o2_2020, title = {H2O2 and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum}, author = {Ir\`{e}ne Amblard and Marion Thauvin and Christine Rampon and Isabelle Queguiner and Valeriy V Pak and Vsevolod Belousov and Alain Prochiantz and Michel Volovitch and Alain Joliot and Sophie Vriz}, url = {https://www.nature.com/articles/s42003-020-01268-7}, doi = {10.1038/s42003-020-01268-7}, issn = {2399-3642}, year = {2020}, date = {2020-01-01}, urldate = {2023-10-31}, journal = {Communications Biology}, volume = {3}, number = {1}, pages = {1--9}, abstract = {Although a physiological role for redox signaling is now clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for H2O2 have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of H2O2 levels disturb cell plasticity and morphogenesis. Here we ask whether endogenous H2O2 could participate in the patterning of the embryo. We find that perturbations of endogenous H2O2 levels impact on the distribution of the Engrailed homeoprotein, a strong determinant of midbrain patterning. Engrailed 2 is secreted from cells with high H2O2 levels and taken up by cells with low H2O2 levels where it leads to increased H2O2 production, steering the directional spread of the Engrailed gradient. These results illustrate the interplay between protein signaling pathways and metabolic processes during morphogenetic events.}, note = {Number: 1 Publisher: Nature Publishing Group}, keywords = {}, pubstate = {published}, tppubtype = {article} } Although a physiological role for redox signaling is now clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for H2O2 have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of H2O2 levels disturb cell plasticity and morphogenesis. Here we ask whether endogenous H2O2 could participate in the patterning of the embryo. We find that perturbations of endogenous H2O2 levels impact on the distribution of the Engrailed homeoprotein, a strong determinant of midbrain patterning. Engrailed 2 is secreted from cells with high H2O2 levels and taken up by cells with low H2O2 levels where it leads to increased H2O2 production, steering the directional spread of the Engrailed gradient. These results illustrate the interplay between protein signaling pathways and metabolic processes during morphogenetic events. |
A Far-Red Emitting Fluorescent Chemogenetic Reporter for In Vivo Molecular Imaging Article de journal Chenge Li; Alison G Tebo; Marion Thauvin; Marie-Aude Plamont; Michel Volovitch; Xavier Morin; Sophie Vriz; Arnaud Gautier Angewandte Chemie International Edition, 59 (41), p. 17917–17923, 2020, ISSN: 1521-3773, (_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202006576). @article{li_far-red_2020, title = {A Far-Red Emitting Fluorescent Chemogenetic Reporter for In Vivo Molecular Imaging}, author = {Chenge Li and Alison G Tebo and Marion Thauvin and Marie-Aude Plamont and Michel Volovitch and Xavier Morin and Sophie Vriz and Arnaud Gautier}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202006576}, doi = {10.1002/anie.202006576}, issn = {1521-3773}, year = {2020}, date = {2020-01-01}, urldate = {2023-10-31}, journal = {Angewandte Chemie International Edition}, volume = {59}, number = {41}, pages = {17917--17923}, abstract = {Far-red emitting fluorescent labels are highly desirable for spectral multiplexing and deep tissue imaging. Here, we describe the generation of frFAST (far-red Fluorescence Activating and absorption Shifting Tag), a 14-kDa monomeric protein that forms a bright far-red fluorescent assembly with (4-hydroxy-3-methoxy-phenyl)allylidene rhodanine (HPAR-3OM). As HPAR-3OM is essentially non-fluorescent in solution and in cells, frFAST can be imaged with high contrast in presence of free HPAR-3OM, which allowed the rapid and efficient imaging of frFAST fusions in live cells, zebrafish embryo/larvae, and chicken embryos. Beyond enabling the genetic encoding of far-red fluorescence, frFAST allowed the design of a far-red chemogenetic reporter of protein\textendashprotein interactions, demonstrating its great potential for the design of innovative far-red emitting biosensors.}, note = {_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202006576}, keywords = {}, pubstate = {published}, tppubtype = {article} } Far-red emitting fluorescent labels are highly desirable for spectral multiplexing and deep tissue imaging. Here, we describe the generation of frFAST (far-red Fluorescence Activating and absorption Shifting Tag), a 14-kDa monomeric protein that forms a bright far-red fluorescent assembly with (4-hydroxy-3-methoxy-phenyl)allylidene rhodanine (HPAR-3OM). As HPAR-3OM is essentially non-fluorescent in solution and in cells, frFAST can be imaged with high contrast in presence of free HPAR-3OM, which allowed the rapid and efficient imaging of frFAST fusions in live cells, zebrafish embryo/larvae, and chicken embryos. Beyond enabling the genetic encoding of far-red fluorescence, frFAST allowed the design of a far-red chemogenetic reporter of protein–protein interactions, demonstrating its great potential for the design of innovative far-red emitting biosensors. |
Rational Design of Fractal Gold Nanosphere Assemblies with Optimized Photothermal Conversion Using a Quantitative Structure Property Relationship (QSPR) Approach Article de journal Alice Balfourier; Vladimir Mulens-Arias; Florence Gazeau; Florent Carn The Journal of Physical Chemistry C, 124 (16), p. 8938–8948, 2020, ISSN: 1932-7447, 1932-7455. @article{balfourier_rational_2020, title = {Rational Design of Fractal Gold Nanosphere Assemblies with Optimized Photothermal Conversion Using a Quantitative Structure Property Relationship (QSPR) Approach}, author = {Alice Balfourier and Vladimir Mulens-Arias and Florence Gazeau and Florent Carn}, url = {https://pubs.acs.org/doi/10.1021/acs.jpcc.0c00384}, doi = {10.1021/acs.jpcc.0c00384}, issn = {1932-7447, 1932-7455}, year = {2020}, date = {2020-01-01}, urldate = {2022-03-31}, journal = {The Journal of Physical Chemistry C}, volume = {124}, number = {16}, pages = {8938--8948}, abstract = {Assemblies of plasmonic nanoparticles have been proposed for various applications, including photothermal therapy, exploiting surface plasmon coupling phenomena. However, the rational design of fractal nanoparticle assembly remains challenging due to the lack of structural characterizations and modelization of real systems. Here we used the quantitative structure property relationship (QSPR) approach, driven by experimental data and statistical analysis, to establish a relationship between structural descriptors of fractal gold nanoparticle (GNP) aggregates and their light-to-heat conversion. A total of 160 assemblies of various size spherical GNPs with different polyelectrolyte chains were synthesized, which differ in their global charge, size, mass fractal dimension, and plasmonic properties. Fifteen independent descriptors of structure and properties were extracted and further analyzed by QSPR. Principal component analysis and multilinear regression reveal that light-to-heat conversion is mainly governed by the structure of the aggregates and not by the characteristics of the building blocks. This highlights the key role of the fractal dimension of the aggregate and of the ratio of GNP/polyelectrolyte mass to optimize photothermal effects. Rational criteria to optimize light-to-heat conversion within nonideal fractal assemblies of GNP were identified, relaxing on the choice of other parameters, such as GNP or aggregate size, that can be adapted to the desired biomedical applications.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Assemblies of plasmonic nanoparticles have been proposed for various applications, including photothermal therapy, exploiting surface plasmon coupling phenomena. However, the rational design of fractal nanoparticle assembly remains challenging due to the lack of structural characterizations and modelization of real systems. Here we used the quantitative structure property relationship (QSPR) approach, driven by experimental data and statistical analysis, to establish a relationship between structural descriptors of fractal gold nanoparticle (GNP) aggregates and their light-to-heat conversion. A total of 160 assemblies of various size spherical GNPs with different polyelectrolyte chains were synthesized, which differ in their global charge, size, mass fractal dimension, and plasmonic properties. Fifteen independent descriptors of structure and properties were extracted and further analyzed by QSPR. Principal component analysis and multilinear regression reveal that light-to-heat conversion is mainly governed by the structure of the aggregates and not by the characteristics of the building blocks. This highlights the key role of the fractal dimension of the aggregate and of the ratio of GNP/polyelectrolyte mass to optimize photothermal effects. Rational criteria to optimize light-to-heat conversion within nonideal fractal assemblies of GNP were identified, relaxing on the choice of other parameters, such as GNP or aggregate size, that can be adapted to the desired biomedical applications. |
Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy Article de journal Hui Shan Liew; Chun-Wai Mai; Mohd Zulkefeli; Thiagarajan Madheswaran; Lik Voon Kiew; Nicolas Delsuc; May Lee Low Molecules, 25 (18), 2020, ISSN: 1420-3049. @article{molecules25184176, title = {Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy}, author = {Hui Shan Liew and Chun-Wai Mai and Mohd Zulkefeli and Thiagarajan Madheswaran and Lik Voon Kiew and Nicolas Delsuc and May Lee Low}, url = {https://www.mdpi.com/1420-3049/25/18/4176}, doi = {10.3390/molecules25184176}, issn = {1420-3049}, year = {2020}, date = {2020-01-01}, journal = {Molecules}, volume = {25}, number = {18}, abstract = {Photodynamic therapy (PDT) is emerging as a significant complementary or alternative approach for cancer treatment. PDT drugs act as photosensitisers, which upon using appropriate wavelength light and in the presence of molecular oxygen, can lead to cell death. Herein, we reviewed the general characteristics of the different generation of photosensitisers. We also outlined the emergence of rhenium (Re) and more specifically, Re(I) tricarbonyl complexes as a new generation of metal-based photosensitisers for photodynamic therapy that are of great interest in multidisciplinary research. The photophysical properties and structures of Re(I) complexes discussed in this review are summarised to determine basic features and similarities among the structures that are important for their phototoxic activity and future investigations. We further examined the in vitro and in vivo efficacies of the Re(I) complexes that have been synthesised for anticancer purposes. We also discussed Re(I) complexes in conjunction with the advancement of two-photon PDT, drug combination study, nanomedicine, and photothermal therapy to overcome the limitation of such complexes, which generally absorb short wavelengths.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Photodynamic therapy (PDT) is emerging as a significant complementary or alternative approach for cancer treatment. PDT drugs act as photosensitisers, which upon using appropriate wavelength light and in the presence of molecular oxygen, can lead to cell death. Herein, we reviewed the general characteristics of the different generation of photosensitisers. We also outlined the emergence of rhenium (Re) and more specifically, Re(I) tricarbonyl complexes as a new generation of metal-based photosensitisers for photodynamic therapy that are of great interest in multidisciplinary research. The photophysical properties and structures of Re(I) complexes discussed in this review are summarised to determine basic features and similarities among the structures that are important for their phototoxic activity and future investigations. We further examined the in vitro and in vivo efficacies of the Re(I) complexes that have been synthesised for anticancer purposes. We also discussed Re(I) complexes in conjunction with the advancement of two-photon PDT, drug combination study, nanomedicine, and photothermal therapy to overcome the limitation of such complexes, which generally absorb short wavelengths. |
Endocytosis-driven gold nanoparticle fractal rearrangement in cells and its influence on photothermal conversion Article de journal Vladimir Mulens-Arias; Alice Balfourier; Alba Nicolás-Boluda; Florent Carn; Florence Gazeau Nanoscale, 12 (42), p. 21832–21849, 2020, ISSN: 2040-3364, 2040-3372. @article{mulens-arias_endocytosis-driven_2020, title = {Endocytosis-driven gold nanoparticle fractal rearrangement in cells and its influence on photothermal conversion}, author = {Vladimir Mulens-Arias and Alice Balfourier and Alba Nicol\'{a}s-Boluda and Florent Carn and Florence Gazeau}, url = {http://xlink.rsc.org/?DOI=D0NR05886F}, doi = {10.1039/D0NR05886F}, issn = {2040-3364, 2040-3372}, year = {2020}, date = {2020-01-01}, urldate = {2022-03-31}, journal = {Nanoscale}, volume = {12}, number = {42}, pages = {21832--21849}, abstract = {Cellular endocytosis and intracellular trafficking of nanoparticles induce dynamic rearrangements that profoundly modify the physical properties of nanoparticle and govern their biological outcomes when activated by external fields. , Cellular endocytosis and intracellular trafficking of nanoparticles induce dynamic rearrangements that profoundly modify the physical properties of nanoparticle and govern their biological outcomes when activated by external fields. The precise structure, organization, distribution, and density of gold nanoparticles (AuNPs) confined within intracellular compartments such as lysosomes have not been studied comprehensively, hampering the derivation of predictive models of their therapeutic activity within the cells of interest. By using transmission electron microscopy and small-angle X-ray scattering, we have determined that canonical spherical citrate-coated AuNPs in the 3\textendash30 nm size range form fractal clusters in endolysosomes of macrophages, endothelial cells, and colon cancer cells. Statistical analysis revealed that the cluster size and endolysosome size are correlated but do not depend on the size of AuNPs unless larger preformed aggregates of AuNPs are internalized. Smaller AuNPs are confined in greater numbers in loose aggregates covering a higher fraction of the endolysosomes compared to the largest AuNPs. The fractal dimensions of intracellular clusters increased with the particle size, regardless of the cell type. We thus analyzed how these intracellular structure parameters of AuNPs affect their optical absorption and photothermal properties. We observed that a 2 nd plasmon resonance band was shifted to the near-infrared region when the nanoparticle size and fractal dimensions of the intracellular cluster increased. This phenomenon of intracellular plasmon coupling is not directly correlated to the size of the intralysosomal cluster or the number of AuNPs per cluster but rather to the compacity of the cluster and the size of the individual AuNPs. The intracellular plasmon-coupling phenomenon translates to an efficient heating efficiency with the excitation of the three cell types at 808 nm, transforming the NIR-transparent canonical AuNPs with sizes below 30 nm into NIR-absorbing clusters in the tumor microenvironment. Harnessing the spontaneous clustering of spherical AuNPs by cells might be a more valuable strategy for theranostic purposes than deploying complex engineering to derive NIR-absorbent nanostructures out of their environment. Our paper sheds light on AuNP intracellular reorganization and proposes a general method to link their intracellular fates to their in situ physical properties exploited in medical applications.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cellular endocytosis and intracellular trafficking of nanoparticles induce dynamic rearrangements that profoundly modify the physical properties of nanoparticle and govern their biological outcomes when activated by external fields. , Cellular endocytosis and intracellular trafficking of nanoparticles induce dynamic rearrangements that profoundly modify the physical properties of nanoparticle and govern their biological outcomes when activated by external fields. The precise structure, organization, distribution, and density of gold nanoparticles (AuNPs) confined within intracellular compartments such as lysosomes have not been studied comprehensively, hampering the derivation of predictive models of their therapeutic activity within the cells of interest. By using transmission electron microscopy and small-angle X-ray scattering, we have determined that canonical spherical citrate-coated AuNPs in the 3–30 nm size range form fractal clusters in endolysosomes of macrophages, endothelial cells, and colon cancer cells. Statistical analysis revealed that the cluster size and endolysosome size are correlated but do not depend on the size of AuNPs unless larger preformed aggregates of AuNPs are internalized. Smaller AuNPs are confined in greater numbers in loose aggregates covering a higher fraction of the endolysosomes compared to the largest AuNPs. The fractal dimensions of intracellular clusters increased with the particle size, regardless of the cell type. We thus analyzed how these intracellular structure parameters of AuNPs affect their optical absorption and photothermal properties. We observed that a 2 nd plasmon resonance band was shifted to the near-infrared region when the nanoparticle size and fractal dimensions of the intracellular cluster increased. This phenomenon of intracellular plasmon coupling is not directly correlated to the size of the intralysosomal cluster or the number of AuNPs per cluster but rather to the compacity of the cluster and the size of the individual AuNPs. The intracellular plasmon-coupling phenomenon translates to an efficient heating efficiency with the excitation of the three cell types at 808 nm, transforming the NIR-transparent canonical AuNPs with sizes below 30 nm into NIR-absorbing clusters in the tumor microenvironment. Harnessing the spontaneous clustering of spherical AuNPs by cells might be a more valuable strategy for theranostic purposes than deploying complex engineering to derive NIR-absorbent nanostructures out of their environment. Our paper sheds light on AuNP intracellular reorganization and proposes a general method to link their intracellular fates to their in situ physical properties exploited in medical applications. |
Ultrasensitive Genetically Encoded Indicator for Hydrogen Peroxide Identifies Roles for the Oxidant in Cell Migration and Mitochondrial Function Article de journal Valeriy V Pak; Daria Ezeriņa; Olga G Lyublinskaya; Brandán Pedre; Pyotr A Tyurin-Kuzmin; Natalie M Mishina; Marion Thauvin; David Young; Khadija Wahni; Santiago Agustín Martínez Gache; Alexandra D Demidovich; Yulia G Ermakova; Yulia D Maslova; Arina G Shokhina; Emrah Eroglu; Dmitry S Bilan; Ivan Bogeski; Thomas Michel; Sophie Vriz; Joris Messens; Vsevolod V Belousov Cell Metabolism, 31 (3), p. 642–653.e6, 2020, ISSN: 1932-7420. @article{pak_ultrasensitive_2020, title = {Ultrasensitive Genetically Encoded Indicator for Hydrogen Peroxide Identifies Roles for the Oxidant in Cell Migration and Mitochondrial Function}, author = {Valeriy V Pak and Daria Ezeri\c{n}a and Olga G Lyublinskaya and Brand\'{a}n Pedre and Pyotr A Tyurin-Kuzmin and Natalie M Mishina and Marion Thauvin and David Young and Khadija Wahni and Santiago Agust\'{i}n Mart\'{i}nez Gache and Alexandra D Demidovich and Yulia G Ermakova and Yulia D Maslova and Arina G Shokhina and Emrah Eroglu and Dmitry S Bilan and Ivan Bogeski and Thomas Michel and Sophie Vriz and Joris Messens and Vsevolod V Belousov}, doi = {10.1016/j.cmet.2020.02.003}, issn = {1932-7420}, year = {2020}, date = {2020-01-01}, journal = {Cell Metabolism}, volume = {31}, number = {3}, pages = {642--653.e6}, abstract = {Hydrogen peroxide (H2O2) is a key redox intermediate generated within cells. Existing probes for H2O2 have not solved the problem of detection of the ultra-low concentrations of the oxidant: these reporters are not sensitive enough, or pH-dependent, or insufficiently bright, or not functional in mammalian cells, or have poor dynamic range. Here we present HyPer7, the first bright, pH-stable, ultrafast, and ultrasensitive ratiometric H2O2 probe. HyPer7 is fully functional in mammalian cells and in other higher eukaryotes. The probe consists of a circularly permuted GFP integrated into the ultrasensitive OxyR domain from Neisseria meningitidis. Using HyPer7, we were able to uncover the details of H2O2 diffusion from the mitochondrial matrix, to find a functional output of H2O2 gradients in polarized cells, and to prove the existence of H2O2 gradients in wounded tissue in vivo. Overall, HyPer7 is a probe of choice for real-time H2O2 imaging in various biological contexts.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Hydrogen peroxide (H2O2) is a key redox intermediate generated within cells. Existing probes for H2O2 have not solved the problem of detection of the ultra-low concentrations of the oxidant: these reporters are not sensitive enough, or pH-dependent, or insufficiently bright, or not functional in mammalian cells, or have poor dynamic range. Here we present HyPer7, the first bright, pH-stable, ultrafast, and ultrasensitive ratiometric H2O2 probe. HyPer7 is fully functional in mammalian cells and in other higher eukaryotes. The probe consists of a circularly permuted GFP integrated into the ultrasensitive OxyR domain from Neisseria meningitidis. Using HyPer7, we were able to uncover the details of H2O2 diffusion from the mitochondrial matrix, to find a functional output of H2O2 gradients in polarized cells, and to prove the existence of H2O2 gradients in wounded tissue in vivo. Overall, HyPer7 is a probe of choice for real-time H2O2 imaging in various biological contexts. |
Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides Article de journal Emilie Mathieu; Anne-Sophie Bernard; Vincent H Y Ching; Andrea Somogyi; Kadda Medjoubi; Jennifer Rodon Fores; Hélène C Bertrand; Amandine Vincent; Sylvain Trépout; Jean-Luc Guerquin-Kern; Andreas Scheitler; Ivana Ivanović-Burmazović; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Dalton Trans., 49 , p. 2323-2330, 2020. @article{C9DT04619Db, title = {Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides}, author = {Emilie Mathieu and Anne-Sophie Bernard and Vincent H Y Ching and Andrea Somogyi and Kadda Medjoubi and Jennifer Rodon Fores and H\'{e}l\`{e}ne C Bertrand and Amandine Vincent and Sylvain Tr\'{e}pout and Jean-Luc Guerquin-Kern and Andreas Scheitler and Ivana Ivanovi\'{c}-Burmazovi\'{c} and Philippe Seksik and Nicolas Delsuc and Clotilde Policar}, url = {http://dx.doi.org/10.1039/C9DT04619D}, doi = {10.1039/C9DT04619D}, year = {2020}, date = {2020-01-01}, journal = {Dalton Trans.}, volume = {49}, pages = {2323-2330}, publisher = {The Royal Society of Chemistry}, abstract = {A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic. |
An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase Article de journal Amandine Vincent; Jennifer Rodon Fores; Elodie Tauziet; Elodie Quévrain; Ágnes Dancs; Amandine Conte-Daban; Anne-Sophie Bernard; Philippe Pelupessy; Koudedja Coulibaly; Philippe Seksik; Christelle Hureau; Katalin Selmeczi; Clotilde Policar; Nicolas Delsuc Chem. Commun., 56 , p. 399-402, 2020. @article{C9CC07920C, title = {An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase}, author = {Amandine Vincent and Jennifer Rodon Fores and Elodie Tauziet and Elodie Qu\'{e}vrain and \'{A}gnes Dancs and Amandine Conte-Daban and Anne-Sophie Bernard and Philippe Pelupessy and Koudedja Coulibaly and Philippe Seksik and Christelle Hureau and Katalin Selmeczi and Clotilde Policar and Nicolas Delsuc}, url = {http://dx.doi.org/10.1039/C9CC07920C}, doi = {10.1039/C9CC07920C}, year = {2020}, date = {2020-01-01}, journal = {Chem. Commun.}, volume = {56}, pages = {399-402}, publisher = {The Royal Society of Chemistry}, abstract = {A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress. |
Differentiation of neural-type cells on multi-scale ordered collagen-silica bionanocomposites Article de journal Nicolas Debons; Dounia Dems; Christophe Hélary; Sylvain Le Grill; Lise Picaut; Flore Renaud; Nicolas Delsuc; Marie-Claire Schanne-Klein; Thibaud Coradin; Carole Aimé Biomater. Sci., 8 , p. 569-576, 2020. @article{C9BM01029Gb, title = {Differentiation of neural-type cells on multi-scale ordered collagen-silica bionanocomposites}, author = {Nicolas Debons and Dounia Dems and Christophe H\'{e}lary and Sylvain Le Grill and Lise Picaut and Flore Renaud and Nicolas Delsuc and Marie-Claire Schanne-Klein and Thibaud Coradin and Carole Aim\'{e}}, url = {http://dx.doi.org/10.1039/C9BM01029G}, doi = {10.1039/C9BM01029G}, year = {2020}, date = {2020-01-01}, journal = {Biomater. Sci.}, volume = {8}, pages = {569-576}, publisher = {The Royal Society of Chemistry}, abstract = {Cells respond to biophysical and biochemical signals. We developed a composite filament from collagen and silica particles modified to interact with collagen and/or present a laminin epitope (IKVAV) crucial for cell\textendashmatrix adhesion and signal transduction. This combines scaffolding and signaling and shows that local tuning of collagen organization enhances cell differentiation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cells respond to biophysical and biochemical signals. We developed a composite filament from collagen and silica particles modified to interact with collagen and/or present a laminin epitope (IKVAV) crucial for cell–matrix adhesion and signal transduction. This combines scaffolding and signaling and shows that local tuning of collagen organization enhances cell differentiation. |
Intracellular location matters: rationalization of the anti-inflammatory activity of a manganese(ii) superoxide dismutase mimic complex Article de journal Emilie Mathieu; Anne-Sophie Bernard; Elodie Quévrain; Martha Zoumpoulaki; Sébastien Iriart; Caroline Lung-Soong; Barry Lai; Kadda Medjoubi; Lucas Henry; Sounderya Nagarajan; Florent Poyer; Andreas Scheitler; Ivana Ivanović-Burmazović; Sergio Marco; Andrea Somogyi; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Chem. Commun., p. -, 2020. @article{D0CC03398G, title = {Intracellular location matters: rationalization of the anti-inflammatory activity of a manganese(ii) superoxide dismutase mimic complex}, author = {Emilie Mathieu and Anne-Sophie Bernard and Elodie Qu\'{e}vrain and Martha Zoumpoulaki and S\'{e}bastien Iriart and Caroline Lung-Soong and Barry Lai and Kadda Medjoubi and Lucas Henry and Sounderya Nagarajan and Florent Poyer and Andreas Scheitler and Ivana Ivanovi\'{c}-Burmazovi\'{c} and Sergio Marco and Andrea Somogyi and Philippe Seksik and Nicolas Delsuc and Clotilde Policar}, url = {http://dx.doi.org/10.1039/D0CC03398G}, doi = {10.1039/D0CC03398G}, year = {2020}, date = {2020-01-01}, journal = {Chem. Commun.}, pages = {-}, publisher = {The Royal Society of Chemistry}, abstract = {A conjugate of a Mn-based superoxide dismutase mimic with a Re-based multimodal probe ̲ was studied in a cellular model of oxidative stress. Its speciation was investigated using Re and Mn X-fluorescence. Interestingly, ̲ shows a distribution different from its unconjugated analogue but a similar concentration in mitochondria and a similar bioactivity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A conjugate of a Mn-based superoxide dismutase mimic with a Re-based multimodal probe ̲ was studied in a cellular model of oxidative stress. Its speciation was investigated using Re and Mn X-fluorescence. Interestingly, ̲ shows a distribution different from its unconjugated analogue but a similar concentration in mitochondria and a similar bioactivity. |
2019 |
Redox Signaling via Lipid Peroxidation Regulates Retinal Progenitor Cell Differentiation Article de journal Shahad Albadri; Federica Naso; Marion Thauvin; Carole Gauron; Carola Parolin; Karine Duroure; Juliette Vougny; Jessica Fiori; Carla Boga; Sophie Vriz; Natalia Calonghi; Filippo Del Bene Developmental Cell, 50 (1), p. 73–89.e6, 2019, ISSN: 1878-1551. @article{albadri_redox_2019, title = {Redox Signaling via Lipid Peroxidation Regulates Retinal Progenitor Cell Differentiation}, author = {Shahad Albadri and Federica Naso and Marion Thauvin and Carole Gauron and Carola Parolin and Karine Duroure and Juliette Vougny and Jessica Fiori and Carla Boga and Sophie Vriz and Natalia Calonghi and Filippo Del Bene}, doi = {10.1016/j.devcel.2019.05.011}, issn = {1878-1551}, year = {2019}, date = {2019-01-01}, journal = {Developmental Cell}, volume = {50}, number = {1}, pages = {73--89.e6}, abstract = {Reactive oxygen species (ROS) and downstream products of lipid oxidation are emerging as important secondary messengers in tissue homeostasis. However, their regulation and mechanism of action remain poorly studied in vivo during normal development. Here, we reveal that the fine regulation of hydrogen peroxide (H2O2) levels by its scavenger Catalase to mediate the switch from proliferation to differentiation in retinal progenitor cells (RPCs) is crucial. We identify 9-hydroxystearic acid (9-HSA), an endogenous downstream lipid peroxidation product, as a mediator of this effect in the zebrafish retina. We show that the 9-HSA proliferative effect is due to the activation of Notch and Wnt pathways through the inhibition of the histone deacetylase 1. We show that the local and temporal manipulation of H2O2 levels in RPCs is sufficient to trigger their premature differentiation. We finally propose a mechanism that links H2O2 homeostasis and neuronal differentiation via the modulation of lipid peroxidation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Reactive oxygen species (ROS) and downstream products of lipid oxidation are emerging as important secondary messengers in tissue homeostasis. However, their regulation and mechanism of action remain poorly studied in vivo during normal development. Here, we reveal that the fine regulation of hydrogen peroxide (H2O2) levels by its scavenger Catalase to mediate the switch from proliferation to differentiation in retinal progenitor cells (RPCs) is crucial. We identify 9-hydroxystearic acid (9-HSA), an endogenous downstream lipid peroxidation product, as a mediator of this effect in the zebrafish retina. We show that the 9-HSA proliferative effect is due to the activation of Notch and Wnt pathways through the inhibition of the histone deacetylase 1. We show that the local and temporal manipulation of H2O2 levels in RPCs is sufficient to trigger their premature differentiation. We finally propose a mechanism that links H2O2 homeostasis and neuronal differentiation via the modulation of lipid peroxidation. |
Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator Article de journal Marie-Anne Guillaumot; Olivier Cerles; Hélène C Bertrand; Evelyne Benoit; Carole Nicco; Sandrine Chouzenoux; Alain Schmitt; Frédéric Batteux; Clotilde Policar; Romain Coriat Oncotarget, 10 (60), p. 6418-6431, 2019, ISSN: 1949-2553. @article{OT27248, title = {Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator}, author = {Marie-Anne Guillaumot and Olivier Cerles and H\'{e}l\`{e}ne C Bertrand and Evelyne Benoit and Carole Nicco and Sandrine Chouzenoux and Alain Schmitt and Fr\'{e}d\'{e}ric Batteux and Clotilde Policar and Romain Coriat}, url = {https://www.oncotarget.com/article/27248/}, doi = {https://doi.org/10.18632/oncotarget.27248}, issn = {1949-2553}, year = {2019}, date = {2019-01-01}, journal = {Oncotarget}, volume = {10}, number = {60}, pages = {6418-6431}, publisher = {Impact Journals, LLC}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Extracellular Pax6 Regulates Tangential Cajal–Retzius Cell Migration in the Developing Mouse Neocortex Article de journal H Kaddour; E Coppola; A A Di Nardo; C Le Poupon; P Mailly; A Wizenmann; M Volovitch; A Prochiantz; A Pierani Cerebral Cortex, p. bhz098, 2019, ISSN: 1047-3211, 1460-2199. @article{kaddour_extracellular_2019, title = {Extracellular Pax6 Regulates Tangential Cajal\textendashRetzius Cell Migration in the Developing Mouse Neocortex}, author = {H Kaddour and E Coppola and A A Di Nardo and C Le Poupon and P Mailly and A Wizenmann and M Volovitch and A Prochiantz and A Pierani}, url = {https://academic.oup.com/cercor/advance-article/doi/10.1093/cercor/bhz098/5513063}, doi = {10.1093/cercor/bhz098}, issn = {1047-3211, 1460-2199}, year = {2019}, date = {2019-01-01}, urldate = {2023-10-31}, journal = {Cerebral Cortex}, pages = {bhz098}, abstract = {The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal\textendashRetzius (CR) neurons by live imaging of f lat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal–Retzius (CR) neurons by live imaging of f lat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development. |
Fatima Hamouri; Weiting Zhang; Isabelle Aujard; Thomas Le Saux; Bertrand Ducos; Sophie Vriz; Ludovic Jullien; David Bensimon Academic Press, 2019. @book{hamouri_chapter_2019, title = {Chapter One - Optical control of protein activity and gene expression by photoactivation of caged cyclofen}, author = {Fatima Hamouri and Weiting Zhang and Isabelle Aujard and Thomas Le Saux and Bertrand Ducos and Sophie Vriz and Ludovic Jullien and David Bensimon}, editor = {Alexander Deiters}, url = {https://www.sciencedirect.com/science/article/pii/S0076687919301247}, doi = {10.1016/bs.mie.2019.04.009}, year = {2019}, date = {2019-01-01}, urldate = {2023-10-31}, booktitle = {Methods in Enzymology}, volume = {624}, pages = {1--23}, publisher = {Academic Press}, series = {Optochemical Biology}, abstract = {The use of light to control the expression of genes and the activity of proteins is a rapidly expanding field. While many of these approaches use a fusion between a light activatable protein and the protein of interest to control the activity of the latter, it is also possible to control the activity of a protein by uncaging a specific ligand. In that context, controlling the activation of a protein fused to the modified estrogen receptor (ERT) by uncaging its ligand cyclofen-OH has emerged as a generic and versatile method to control the activation of proteins quantitatively, quickly and locally in a live organism. Here, we present the experimental details behind this approach.}, keywords = {}, pubstate = {published}, tppubtype = {book} } The use of light to control the expression of genes and the activity of proteins is a rapidly expanding field. While many of these approaches use a fusion between a light activatable protein and the protein of interest to control the activity of the latter, it is also possible to control the activity of a protein by uncaging a specific ligand. In that context, controlling the activation of a protein fused to the modified estrogen receptor (ERT) by uncaging its ligand cyclofen-OH has emerged as a generic and versatile method to control the activation of proteins quantitatively, quickly and locally in a live organism. Here, we present the experimental details behind this approach. |
Disturbance of adhesomes by gold nanoparticles reveals a size- and cell type-bias Article de journal Vladimir Mulens-Arias; Alice Balfourier; Alba Nicolás-Boluda; Florent Carn; Florence Gazeau Biomaterials Science, 7 (1), p. 389–408, 2019, ISSN: 2047-4830, 2047-4849. @article{mulens-arias_disturbance_2019, title = {Disturbance of adhesomes by gold nanoparticles reveals a size- and cell type-bias}, author = {Vladimir Mulens-Arias and Alice Balfourier and Alba Nicol\'{a}s-Boluda and Florent Carn and Florence Gazeau}, url = {http://xlink.rsc.org/?DOI=C8BM01267A}, doi = {10.1039/C8BM01267A}, issn = {2047-4830, 2047-4849}, year = {2019}, date = {2019-01-01}, urldate = {2022-03-31}, journal = {Biomaterials Science}, volume = {7}, number = {1}, pages = {389--408}, abstract = {Gold nanoparticles are known multifunctional theranosis agents. Here, we studied the collective dynamics of adhesive F-actin rich structures upon AuNP treatment. , Gold nanoparticles (AuNP) have been thoroughly studied as multifunctional theranosis agents for cell imaging and cancer therapy as well as sensors due to their tunable physical and chemical properties. Although AuNP have proved to be safe in a wide concentration range, yet other important biological effects can arise in the sublethal window of treatment. This is especially pivotal to understand how AuNP can affect cell biology when labeling steps are needed for cell tracking in vivo , as nanoparticle loading can affect cell migratory/invasion ability, a function mediated by filamentous actin-rich nanometric structures collectively called adhesomes. It is noteworthy that, although numerous research studies have addressed the cell response to AuNP loading, yet none of them focuses on adhesome dynamics as a target of intracellular pathways affected by AuNP. We intend to study the collective dynamics of adhesive F-actin rich structures upon AuNP treatment as an approach to understand the complex AuNP-triggered modulation of migration/invasion related cellular functions. We demonstrated that citrate-coated spherical AuNP of different sizes (3, 11, 16, 30 and 40 nm) disturbed podosome-forming rosettes and the resulting extracellular matrix (ECM) degradation in a murine macrophage model depending on core size. This phenomenon was accompanied by a reduction in metalloproteinase MMP2 and an increment in metalloproteinase inhibitors, TIMP-1/2 and SerpinE1. We also found that AuNP treatment has opposite effects on focal adhesions (FA) in endothelial and mesenchymal stem cells. While endothelial cells reduced their mature FA number and ECM degradation rate upon AuNP treatment, mouse mesenchymal stem cells increased the number and size of mature FA and, therefore, the ECM degradation rate. Overall, AuNP appear to disturb adhesive structures and therefore migratory/invasive cell functions measured as ECM degradation ability, providing new insights into AuNP\textendashcell interaction depending on cell type.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Gold nanoparticles are known multifunctional theranosis agents. Here, we studied the collective dynamics of adhesive F-actin rich structures upon AuNP treatment. , Gold nanoparticles (AuNP) have been thoroughly studied as multifunctional theranosis agents for cell imaging and cancer therapy as well as sensors due to their tunable physical and chemical properties. Although AuNP have proved to be safe in a wide concentration range, yet other important biological effects can arise in the sublethal window of treatment. This is especially pivotal to understand how AuNP can affect cell biology when labeling steps are needed for cell tracking in vivo , as nanoparticle loading can affect cell migratory/invasion ability, a function mediated by filamentous actin-rich nanometric structures collectively called adhesomes. It is noteworthy that, although numerous research studies have addressed the cell response to AuNP loading, yet none of them focuses on adhesome dynamics as a target of intracellular pathways affected by AuNP. We intend to study the collective dynamics of adhesive F-actin rich structures upon AuNP treatment as an approach to understand the complex AuNP-triggered modulation of migration/invasion related cellular functions. We demonstrated that citrate-coated spherical AuNP of different sizes (3, 11, 16, 30 and 40 nm) disturbed podosome-forming rosettes and the resulting extracellular matrix (ECM) degradation in a murine macrophage model depending on core size. This phenomenon was accompanied by a reduction in metalloproteinase MMP2 and an increment in metalloproteinase inhibitors, TIMP-1/2 and SerpinE1. We also found that AuNP treatment has opposite effects on focal adhesions (FA) in endothelial and mesenchymal stem cells. While endothelial cells reduced their mature FA number and ECM degradation rate upon AuNP treatment, mouse mesenchymal stem cells increased the number and size of mature FA and, therefore, the ECM degradation rate. Overall, AuNP appear to disturb adhesive structures and therefore migratory/invasive cell functions measured as ECM degradation ability, providing new insights into AuNP–cell interaction depending on cell type. |