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))
2020 |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
2019 |
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. |
An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra Article de journal Matthias C Vogg; Leonardo Beccari; Laura Iglesias Ollé; Christine Rampon; Sophie Vriz; Chrystelle Perruchoud; Yvan Wenger; Brigitte Galliot Nature Communications, 10 (1), p. 312, 2019, ISSN: 2041-1723, (Number: 1 Publisher: Nature Publishing Group). @article{vogg_evolutionarily-conserved_2019, title = {An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra}, author = {Matthias C Vogg and Leonardo Beccari and Laura Iglesias Oll\'{e} and Christine Rampon and Sophie Vriz and Chrystelle Perruchoud and Yvan Wenger and Brigitte Galliot}, url = {https://www.nature.com/articles/s41467-018-08242-2}, doi = {10.1038/s41467-018-08242-2}, issn = {2041-1723}, year = {2019}, date = {2019-01-01}, urldate = {2023-10-31}, journal = {Nature Communications}, volume = {10}, number = {1}, pages = {312}, abstract = {Polyps of the cnidarian Hydra maintain their adult anatomy through two developmental organizers, the head organizer located apically and the foot organizer basally. The head organizer is made of two antagonistic cross-reacting components, an activator, driving apical differentiation and an inhibitor, preventing ectopic head formation. Here we characterize the head inhibitor by comparing planarian genes down-regulated when β-catenin is silenced to Hydra genes displaying a graded apical-to-basal expression and an up-regulation during head regeneration. We identify Sp5 as a transcription factor that fulfills the head inhibitor properties: leading to a robust multiheaded phenotype when knocked-down in Hydra, acting as a transcriptional repressor of Wnt3 and positively regulated by Wnt/β-catenin signaling. Hydra and zebrafish Sp5 repress Wnt3 promoter activity while Hydra Sp5 also activates its own expression, likely via β-catenin/TCF interaction. This work identifies Sp5 as a potent feedback loop inhibitor of Wnt/β-catenin signaling, a function conserved across eumetazoan evolution.}, note = {Number: 1 Publisher: Nature Publishing Group}, keywords = {}, pubstate = {published}, tppubtype = {article} } Polyps of the cnidarian Hydra maintain their adult anatomy through two developmental organizers, the head organizer located apically and the foot organizer basally. The head organizer is made of two antagonistic cross-reacting components, an activator, driving apical differentiation and an inhibitor, preventing ectopic head formation. Here we characterize the head inhibitor by comparing planarian genes down-regulated when β-catenin is silenced to Hydra genes displaying a graded apical-to-basal expression and an up-regulation during head regeneration. We identify Sp5 as a transcription factor that fulfills the head inhibitor properties: leading to a robust multiheaded phenotype when knocked-down in Hydra, acting as a transcriptional repressor of Wnt3 and positively regulated by Wnt/β-catenin signaling. Hydra and zebrafish Sp5 repress Wnt3 promoter activity while Hydra Sp5 also activates its own expression, likely via β-catenin/TCF interaction. This work identifies Sp5 as a potent feedback loop inhibitor of Wnt/β-catenin signaling, a function conserved across eumetazoan evolution. |
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. |
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. |
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. |
Polyethyleneimine-assisted one-pot synthesis of quasi-fractal plasmonic gold nanocomposites as a photothermal theranostic agent Article de journal Vladimir Mulens-Arias; Alba Nicolás-Boluda; Alexandre Gehanno; Alice Balfourier; Florent Carn; Florence Gazeau Nanoscale, 11 (7), p. 3344–3359, 2019, ISSN: 2040-3372, (Publisher: The Royal Society of Chemistry). @article{mulens-arias_polyethyleneimine-assisted_2019, title = {Polyethyleneimine-assisted one-pot synthesis of quasi-fractal plasmonic gold nanocomposites as a photothermal theranostic agent}, author = {Vladimir Mulens-Arias and Alba Nicol\'{a}s-Boluda and Alexandre Gehanno and Alice Balfourier and Florent Carn and Florence Gazeau}, url = {https://pubs.rsc.org/en/content/articlelanding/2019/nr/c8nr09849b}, doi = {10.1039/C8NR09849B}, issn = {2040-3372}, year = {2019}, date = {2019-01-01}, urldate = {2022-03-30}, journal = {Nanoscale}, volume = {11}, number = {7}, pages = {3344--3359}, abstract = {Gold nanoparticles have been thoroughly used in designing thermal ablative therapies and in photoacoustic imaging in cancer treatment owing to their unique and tunable plasmonic properties. While the plasmonic properties highly depend on the size and structure, controllable aggregation of gold nanoparticles can trigger a plasmonic coupling of adjacent electronic clouds, henceforth leading to an increase of light absorption within the near-infrared (NIR) window. Polymer-engraftment of gold nanoparticles has been investigated to achieve the plasmonic coupling phenomenon, but complex chemical steps are often needed to accomplish a biomedically relevant product. An appealing and controllable manner of achieving polymer-based plasmon coupling is a template-assisted Au+3 reduction that ensures in situ gold reduction and coalescence. Among the polymers exploited as reducing agents are polyethyleneimines (PEI). In this study, we addressed the PEI-assisted synthesis of gold nanoparticles and their further aggregation to obtain fractal NIR-absorbent plasmonic nanoaggregates for photothermal therapy and photoacoustic imaging of colorectal cancer. PEI-assisted Au+3 reduction was followed up by UV-visible light absorption, small-angle X-ray scattering (SAXS), and photo-thermal conversion. The reaction kinetics, stability, and the photothermal plasmonic properties of the as-synthesized nanocomposites tightly depended on the PEI : Au ratio. We defined a PEI-Au ratio range (2.5\textendash5) for the one-pot synthesis of gold nanoparticles that self-arrange into fractal nanoaggregates with demonstrated photo-thermal therapeutic and imaging efficiency both in vitro and in vivo in a colorectal carcinoma (CRC) animal model.}, note = {Publisher: The Royal Society of Chemistry}, keywords = {}, pubstate = {published}, tppubtype = {article} } Gold nanoparticles have been thoroughly used in designing thermal ablative therapies and in photoacoustic imaging in cancer treatment owing to their unique and tunable plasmonic properties. While the plasmonic properties highly depend on the size and structure, controllable aggregation of gold nanoparticles can trigger a plasmonic coupling of adjacent electronic clouds, henceforth leading to an increase of light absorption within the near-infrared (NIR) window. Polymer-engraftment of gold nanoparticles has been investigated to achieve the plasmonic coupling phenomenon, but complex chemical steps are often needed to accomplish a biomedically relevant product. An appealing and controllable manner of achieving polymer-based plasmon coupling is a template-assisted Au+3 reduction that ensures in situ gold reduction and coalescence. Among the polymers exploited as reducing agents are polyethyleneimines (PEI). In this study, we addressed the PEI-assisted synthesis of gold nanoparticles and their further aggregation to obtain fractal NIR-absorbent plasmonic nanoaggregates for photothermal therapy and photoacoustic imaging of colorectal cancer. PEI-assisted Au+3 reduction was followed up by UV-visible light absorption, small-angle X-ray scattering (SAXS), and photo-thermal conversion. The reaction kinetics, stability, and the photothermal plasmonic properties of the as-synthesized nanocomposites tightly depended on the PEI : Au ratio. We defined a PEI-Au ratio range (2.5–5) for the one-pot synthesis of gold nanoparticles that self-arrange into fractal nanoaggregates with demonstrated photo-thermal therapeutic and imaging efficiency both in vitro and in vivo in a colorectal carcinoma (CRC) animal model. |
2018 |
From Naproxen Repurposing to Naproxen Analogues and Their Antiviral Activity against Influenza A Virus Article de journal Sébastien Dilly; Aurélien Fotso Fotso; Nathalie Lejal; Gloria Zedda; Mohamad Chebbo; Fryad Rahman; Simon Companys; Hélène C Bertrand; Jasmina Vidic; Magali Noiray; Marie-Christine Alessi; Bogdan Tarus; Stéphane Quideau; Béatrice Riteau; Anny Slama-Schwok Journal of Medicinal Chemistry, 61 (16), p. 7202–7217, 2018, ISSN: 0022-2623. @article{Dilly2018, title = {From Naproxen Repurposing to Naproxen Analogues and Their Antiviral Activity against Influenza A Virus}, author = {S\'{e}bastien Dilly and Aur\'{e}lien {Fotso Fotso} and Nathalie Lejal and Gloria Zedda and Mohamad Chebbo and Fryad Rahman and Simon Companys and H\'{e}l{\`{e}}ne C Bertrand and Jasmina Vidic and Magali Noiray and Marie-Christine Alessi and Bogdan Tarus and St\'{e}phane Quideau and B\'{e}atrice Riteau and Anny Slama-Schwok}, url = {https://doi.org/10.1021/acs.jmedchem.8b00557}, doi = {10.1021/acs.jmedchem.8b00557}, issn = {0022-2623}, year = {2018}, date = {2018-08-01}, journal = {Journal of Medicinal Chemistry}, volume = {61}, number = {16}, pages = {7202--7217}, publisher = {American Chemical Society}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury Article de journal E Le Moal; G Juban; A S Bernard; T Varga; C Policar; B Chazaud; R Mounier Free Radical Biology and Medicine, 120 , p. 33–40, 2018. @article{LeMoal:2018, title = {Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury}, author = {E Le Moal and G Juban and A S Bernard and T Varga and C Policar and B Chazaud and R Mounier}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044047057&doi=10.1016%2fj.freeradbiomed.2018.02.024&partnerID=40&md5=3d7a016c57bd52dfee180ac22ee70ae8}, doi = {10.1016/j.freeradbiomed.2018.02.024}, year = {2018}, date = {2018-01-01}, journal = {Free Radical Biology and Medicine}, volume = {120}, pages = {33--40}, abstract = {Macrophages are key players of immunity that display different functions according to their activation states. In a regenerative context, pro-inflammatory macrophages (Ly6Cpos) are involved in the mounting of the inflammatory response whereas anti-inflammatory macrophages (Ly6Cneg) dampen the inflammation and promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of tissue injury and of subsequent inflammation as described in a bacterial challenge context. However, whether macrophages produce ROS following a sterile tissue injury is uncertain. In this study, we used complementary in vitro, ex vivo and in vivo experiments in mouse to show that macrophages do not release ROS following a sterile injury in skeletal muscle. Furthermore, expression profiles of genes involved in the response to oxidative stress in Ly6Cpos and Ly6Cneg macrophage subsets did not indicate any antioxidant response in this context. Finally, in vivo, pharmacological antioxidant supplementation with N-Acetyl-cysteine (NAC) following skeletal muscle injury did not alter macrophage phenotype during skeletal muscle regeneration. Overall, these results indicate that following a sterile injury, macrophage-derived ROS release is not involved in the regulation of the inflammatory response in the regenerating skeletal muscle. © 2018 Elsevier Inc.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Macrophages are key players of immunity that display different functions according to their activation states. In a regenerative context, pro-inflammatory macrophages (Ly6Cpos) are involved in the mounting of the inflammatory response whereas anti-inflammatory macrophages (Ly6Cneg) dampen the inflammation and promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of tissue injury and of subsequent inflammation as described in a bacterial challenge context. However, whether macrophages produce ROS following a sterile tissue injury is uncertain. In this study, we used complementary in vitro, ex vivo and in vivo experiments in mouse to show that macrophages do not release ROS following a sterile injury in skeletal muscle. Furthermore, expression profiles of genes involved in the response to oxidative stress in Ly6Cpos and Ly6Cneg macrophage subsets did not indicate any antioxidant response in this context. Finally, in vivo, pharmacological antioxidant supplementation with N-Acetyl-cysteine (NAC) following skeletal muscle injury did not alter macrophage phenotype during skeletal muscle regeneration. Overall, these results indicate that following a sterile injury, macrophage-derived ROS release is not involved in the regulation of the inflammatory response in the regenerating skeletal muscle. © 2018 Elsevier Inc. |
A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease Article de journal A Conte-Daban; V Ambike; R Guillot; N Delsuc; C Policar; C Hureau Chemistry - A European Journal, 24 (20), p. 5095–5099, 2018. @article{Conte-Daban:2018, title = {A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease}, author = {A Conte-Daban and V Ambike and R Guillot and N Delsuc and C Policar and C Hureau}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045131927&doi=10.1002%2fchem.201706049&partnerID=40&md5=5dc310a9e12535e296ba5429250159d3}, doi = {10.1002/chem.201706049}, year = {2018}, date = {2018-01-01}, journal = {Chemistry - A European Journal}, volume = {24}, number = {20}, pages = {5095--5099}, abstract = {Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a MnII-based superoxide dismutase (SOD) mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target CuII-associated events, namely, CuII-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1+ is able to remove CuII from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a MnII-based superoxide dismutase (SOD) mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target CuII-associated events, namely, CuII-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1+ is able to remove CuII from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging Article de journal L Henry; N Delsuc; C Laugel; F Lambert; C Sandt; S Hostachy; A -S Bernard; H C Bertrand; L Grimaud; A Baillet-Guffroy; C Policar Bioconjugate Chemistry, 29 (4), p. 987–991, 2018. @article{Henry:2018, title = {Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging}, author = {L Henry and N Delsuc and C Laugel and F Lambert and C Sandt and S Hostachy and A -S Bernard and H C Bertrand and L Grimaud and A Baillet-Guffroy and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045549363&doi=10.1021%2facs.bioconjchem.7b00825&partnerID=40&md5=87140714a264358836c5f4c7734e49a3}, doi = {10.1021/acs.bioconjchem.7b00825}, year = {2018}, date = {2018-01-01}, journal = {Bioconjugate Chemistry}, volume = {29}, number = {4}, pages = {987--991}, abstract = {Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin. © 2018 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin. © 2018 American Chemical Society. |
Fluorogenic Probing of Membrane Protein Trafficking Article de journal C Li; A Mourton; M -A Plamont; V Rodrigues; I Aujard; M Volovitch; T Le Saux; F Perez; S Vriz; L Jullien; A Joliot; A Gautier Bioconjugate Chemistry, 29 (6), p. 1823–1828, 2018. @article{Li:2018a, title = {Fluorogenic Probing of Membrane Protein Trafficking}, author = {C Li and A Mourton and M -A Plamont and V Rodrigues and I Aujard and M Volovitch and T Le Saux and F Perez and S Vriz and L Jullien and A Joliot and A Gautier}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047641063&doi=10.1021%2facs.bioconjchem.8b00180&partnerID=40&md5=bcbb74499b742fa8b0762b8c52ebf5dd}, doi = {10.1021/acs.bioconjchem.8b00180}, year = {2018}, date = {2018-01-01}, journal = {Bioconjugate Chemistry}, volume = {29}, number = {6}, pages = {1823--1828}, abstract = {Methods to differentially label cell-surface and intracellular membrane proteins are indispensable for understanding their function and the regulation of their trafficking. We present an efficient strategy for the rapid and selective fluorescent labeling of membrane proteins based on the chemical-genetic fluorescent marker FAST (fluorescence-activating and absorption-shifting tag). Cell-surface FAST-tagged proteins could be selectively and rapidly labeled using fluorogenic membrane-impermeant 4-hydroxybenzylidene rhodanine (HBR) analogs. This approach allows the study of protein trafficking at the plasma membrane with various fluorometric techniques, and opens exciting prospects for the high-throughput screening of small molecules able to restore disease-related trafficking defects. © 2018 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Methods to differentially label cell-surface and intracellular membrane proteins are indispensable for understanding their function and the regulation of their trafficking. We present an efficient strategy for the rapid and selective fluorescent labeling of membrane proteins based on the chemical-genetic fluorescent marker FAST (fluorescence-activating and absorption-shifting tag). Cell-surface FAST-tagged proteins could be selectively and rapidly labeled using fluorogenic membrane-impermeant 4-hydroxybenzylidene rhodanine (HBR) analogs. This approach allows the study of protein trafficking at the plasma membrane with various fluorometric techniques, and opens exciting prospects for the high-throughput screening of small molecules able to restore disease-related trafficking defects. © 2018 American Chemical Society. |
Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins Article de journal S Hostachy; M Masuda; T Miki; I Hamachi; S Sagan; O Lequin; K Medjoubi; A Somogyi; N Delsuc; C Policar Chemical Science, 9 (19), p. 4483–4487, 2018. @article{Hostachy:2018, title = {Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins}, author = {S Hostachy and M Masuda and T Miki and I Hamachi and S Sagan and O Lequin and K Medjoubi and A Somogyi and N Delsuc and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047244059&doi=10.1039%2fc8sc00886h&partnerID=40&md5=4625eaa891ccc665a2357b73e20e3541}, doi = {10.1039/c8sc00886h}, year = {2018}, date = {2018-01-01}, journal = {Chemical Science}, volume = {9}, number = {19}, pages = {4483--4487}, abstract = {Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements (Z ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags. In this work, we study rhenium complexes as a convenient and sensitive probe for X-ray fluorescence microspectroscopy. We demonstrate their ability to label and sense exogenously incubated or endogenous proteins inside cells. © The Royal Society of Chemistry 2018.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements (Z ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags. In this work, we study rhenium complexes as a convenient and sensitive probe for X-ray fluorescence microspectroscopy. We demonstrate their ability to label and sense exogenously incubated or endogenous proteins inside cells. © The Royal Society of Chemistry 2018. |
Opioids prevent regeneration in adult mammals through inhibition of ROS production Article de journal Elodie Labit; Lise Rabiller; Christine Rampon; Christophe Guissard; Mireille André; Corinne Barreau; Béatrice Cousin; Audrey Carrière; Mohamad Ala Eddine; Bernard Pipy; Luc Pénicaud; Anne Lorsignol; Sophie Vriz; Cécile Dromard; Louis Casteilla Scientific Reports, 8 (1), p. 12170, 2018, ISSN: 2045-2322. @article{labit_opioids_2018, title = {Opioids prevent regeneration in adult mammals through inhibition of ROS production}, author = {Elodie Labit and Lise Rabiller and Christine Rampon and Christophe Guissard and Mireille Andr\'{e} and Corinne Barreau and B\'{e}atrice Cousin and Audrey Carri\`{e}re and Mohamad Ala Eddine and Bernard Pipy and Luc P\'{e}nicaud and Anne Lorsignol and Sophie Vriz and C\'{e}cile Dromard and Louis Casteilla}, doi = {10.1038/s41598-018-29594-1}, issn = {2045-2322}, year = {2018}, date = {2018-01-01}, journal = {Scientific Reports}, volume = {8}, number = {1}, pages = {12170}, abstract = {Inhibition of regeneration and induction of tissue fibrosis are classic outcomes of tissue repair in adult mammals. Here, using a newly developed model of regeneration in adult mammals i.e. regeneration after massive resection of an inguinal fat pad, we demonstrate that both endogenous and exogenous opioids prevent tissue regeneration in adults, by inhibiting the early production of reactive oxygen species (ROS) that generally occurs after lesion and is required for regeneration. These effects can be overcome and regeneration induced by the use of an opioid antagonist. The results obtained in both our new model and the gold standard adult zebrafish demonstrate that this mechanism can be considered as a general paradigm in vertebrates. This work clearly demonstrates that ROS is required for tissue regeneration in adult mammals and shows the deleterious effect of opioids on tissue regeneration through the control of this ROS production. It thus raises questions about opioid-based analgesia in perioperative care.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Inhibition of regeneration and induction of tissue fibrosis are classic outcomes of tissue repair in adult mammals. Here, using a newly developed model of regeneration in adult mammals i.e. regeneration after massive resection of an inguinal fat pad, we demonstrate that both endogenous and exogenous opioids prevent tissue regeneration in adults, by inhibiting the early production of reactive oxygen species (ROS) that generally occurs after lesion and is required for regeneration. These effects can be overcome and regeneration induced by the use of an opioid antagonist. The results obtained in both our new model and the gold standard adult zebrafish demonstrate that this mechanism can be considered as a general paradigm in vertebrates. This work clearly demonstrates that ROS is required for tissue regeneration in adult mammals and shows the deleterious effect of opioids on tissue regeneration through the control of this ROS production. It thus raises questions about opioid-based analgesia in perioperative care. |
Control of Protein Activity and Gene Expression by Cyclofen-OH Uncaging Article de journal W Zhang; F Hamouri; Z Feng; I Aujard; B Ducos; S Ye; S Weiss; M Volovitch; S Vriz; L Jullien; D Bensimon ChemBioChem, 19 (12), p. 1232–1238, 2018. @article{Zhang:2018, title = {Control of Protein Activity and Gene Expression by Cyclofen-OH Uncaging}, author = {W Zhang and F Hamouri and Z Feng and I Aujard and B Ducos and S Ye and S Weiss and M Volovitch and S Vriz and L Jullien and D Bensimon}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042596408&doi=10.1002%2fcbic.201700630&partnerID=40&md5=e4da60b83f338aba093989913695947b}, doi = {10.1002/cbic.201700630}, year = {2018}, date = {2018-01-01}, journal = {ChemBioChem}, volume = {19}, number = {12}, pages = {1232--1238}, abstract = {The use of light to control the expression of genes and the activity of proteins is a rapidly expanding field. Whereas many of these approaches use fusion between a light-activable 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. We present that approach and its uses in a variety of physiological contexts. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } The use of light to control the expression of genes and the activity of proteins is a rapidly expanding field. Whereas many of these approaches use fusion between a light-activable 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. We present that approach and its uses in a variety of physiological contexts. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
Rhenium tricarbonyl complexes with arenethiolate axial ligands Article de journal M He; H Y V Ching; C Policar; H C Bertrand New Journal of Chemistry, 42 (14), p. 11312–11323, 2018. @article{He:2018, title = {Rhenium tricarbonyl complexes with arenethiolate axial ligands}, author = {M He and H Y V Ching and C Policar and H C Bertrand}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85049750977&doi=10.1039%2fc8nj01960f&partnerID=40&md5=eac4613cb3f849f5a149c72a46384912}, doi = {10.1039/c8nj01960f}, year = {2018}, date = {2018-01-01}, journal = {New Journal of Chemistry}, volume = {42}, number = {14}, pages = {11312--11323}, abstract = {Due to their unique electronic and photophysical properties, rhenium(i) fac-tricarbonyl complexes of general formula [Re(NtextasciicircumN)(CO)3X]n+ have been arousing constant interest in many diverse fields and applications, such as CO2 (photo)electroreduction, organic light emitting diodes and materials, sensors, biological applications and bio-imaging. The photophysical properties of [Re(NtextasciicircumN)(CO)3X]n+ complexes can be modulated by structural variations of the ligands. Modifications of the NtextasciicircumN diimine ligand and of the axial X ligand have been deeply investigated. However, thiolate ligands have scarcely been used in the synthesis of rhenium tricarbonyl complexes. We describe the synthesis of a series of Pyta and Tapy-based Re(i) fac-tricarbonyl complexes with diversely para-substituted arenethiolates in the coordination sphere and report on the electrochemical, photophysical properties and DFT studies of such complexes. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Due to their unique electronic and photophysical properties, rhenium(i) fac-tricarbonyl complexes of general formula [Re(NtextasciicircumN)(CO)3X]n+ have been arousing constant interest in many diverse fields and applications, such as CO2 (photo)electroreduction, organic light emitting diodes and materials, sensors, biological applications and bio-imaging. The photophysical properties of [Re(NtextasciicircumN)(CO)3X]n+ complexes can be modulated by structural variations of the ligands. Modifications of the NtextasciicircumN diimine ligand and of the axial X ligand have been deeply investigated. However, thiolate ligands have scarcely been used in the synthesis of rhenium tricarbonyl complexes. We describe the synthesis of a series of Pyta and Tapy-based Re(i) fac-tricarbonyl complexes with diversely para-substituted arenethiolates in the coordination sphere and report on the electrochemical, photophysical properties and DFT studies of such complexes. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique. |
Hydrogen Peroxide and Redox Regulation of Developments Article de journal Christine Rampon; Michel Volovitch; Alain Joliot; Sophie Vriz Antioxidants, 7 (11), 2018, ISSN: 2076-3921. @article{antiox7110159, title = {Hydrogen Peroxide and Redox Regulation of Developments}, author = {Christine Rampon and Michel Volovitch and Alain Joliot and Sophie Vriz}, url = {https://www.mdpi.com/2076-3921/7/11/159}, doi = {10.3390/antiox7110159}, issn = {2076-3921}, year = {2018}, date = {2018-01-01}, journal = {Antioxidants}, volume = {7}, number = {11}, abstract = {Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS, endowed with signalling properties, are mainly produced by NADPH oxidases (NOXs) at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differ in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic, in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetic processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function, as well as pharmacological strategies, have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS, endowed with signalling properties, are mainly produced by NADPH oxidases (NOXs) at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differ in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic, in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetic processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function, as well as pharmacological strategies, have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways. |
Clarifying the Copper Coordination Environment in a de Novo Designed Red Copper Protein Article de journal K J Koebke; L Ruckthong; J L Meagher; E Mathieu; J Harland; A Deb; N Lehnert; C Policar; C Tard; J E Penner-Hahn; J A Stuckey; V L Pecoraro Inorganic Chemistry, 57 (19), p. 12291–12302, 2018. @article{Koebke:2018, title = {Clarifying the Copper Coordination Environment in a de Novo Designed Red Copper Protein}, author = {K J Koebke and L Ruckthong and J L Meagher and E Mathieu and J Harland and A Deb and N Lehnert and C Policar and C Tard and J E Penner-Hahn and J A Stuckey and V L Pecoraro}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85053716026&doi=10.1021%2facs.inorgchem.8b01989&partnerID=40&md5=1ff4fcf88039da93326134a5ecf32822}, doi = {10.1021/acs.inorgchem.8b01989}, year = {2018}, date = {2018-01-01}, journal = {Inorganic Chemistry}, volume = {57}, number = {19}, pages = {12291--12302}, abstract = {Cupredoxins are copper-dependent electron-transfer proteins that can be categorized as blue, purple, green, and red depending on the spectroscopic properties of the Cu(II) bound forms. Interestingly, despite significantly different first coordination spheres and nuclearity, all cupredoxins share a common Greek Key β-sheet fold. We have previously reported the design of a red copper protein within a completely distinct three-helical bundle protein, α3DChC2.(1)While this design demonstrated that a β-barrel fold was not requisite to recapitulate the properties of a native cupredoxin center, the parent peptide α3D was not sufficiently stable to allow further study through additional mutations. Here we present the design of an elongated protein GRANDα3D (GRα3D) with ΔGu = -11.4 kcal/mol compared to the original design's -5.1 kcal/mol. Diffraction quality crystals were grown of GRα3D (a first for an α3D peptide) and solved to a resolution of 1.34 r{A}. Examination of this structure suggested that Glu41 might interact with the Cu in our previously reported red copper protein. The previous bis(histidine)(cysteine) site (GRα3DChC2) was designed into this new scaffold and a series of variant constructs were made to explore this hypothesis. Mutation studies around Glu41 not only prove the proposed interaction, but also enabled tuning of the constructs' hyperfine coupling constant from 160 to 127 × 10-4 cm-1. X-ray absorption spectroscopy analysis is consistent with these hyperfine coupling differences being the result of variant 4p mixing related to coordination geometry changes. These studies not only prove that an Glu41-Cu interaction leads to the α3DChC2 construct's red copper protein like spectral properties, but also exemplify the exact control one can have in a de novo construct to tune the properties of an electron-transfer Cu site. Copyright © 2018 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cupredoxins are copper-dependent electron-transfer proteins that can be categorized as blue, purple, green, and red depending on the spectroscopic properties of the Cu(II) bound forms. Interestingly, despite significantly different first coordination spheres and nuclearity, all cupredoxins share a common Greek Key β-sheet fold. We have previously reported the design of a red copper protein within a completely distinct three-helical bundle protein, α3DChC2.(1)While this design demonstrated that a β-barrel fold was not requisite to recapitulate the properties of a native cupredoxin center, the parent peptide α3D was not sufficiently stable to allow further study through additional mutations. Here we present the design of an elongated protein GRANDα3D (GRα3D) with ΔGu = -11.4 kcal/mol compared to the original design's -5.1 kcal/mol. Diffraction quality crystals were grown of GRα3D (a first for an α3D peptide) and solved to a resolution of 1.34 Å. Examination of this structure suggested that Glu41 might interact with the Cu in our previously reported red copper protein. The previous bis(histidine)(cysteine) site (GRα3DChC2) was designed into this new scaffold and a series of variant constructs were made to explore this hypothesis. Mutation studies around Glu41 not only prove the proposed interaction, but also enabled tuning of the constructs' hyperfine coupling constant from 160 to 127 × 10-4 cm-1. X-ray absorption spectroscopy analysis is consistent with these hyperfine coupling differences being the result of variant 4p mixing related to coordination geometry changes. These studies not only prove that an Glu41-Cu interaction leads to the α3DChC2 construct's red copper protein like spectral properties, but also exemplify the exact control one can have in a de novo construct to tune the properties of an electron-transfer Cu site. Copyright © 2018 American Chemical Society. |
Increased Efficiency of Dye-Sensitized Solar Cells by Incorporation of a π Spacer in Donor–Acceptor Zinc Porphyrins Bearing Cyanoacrylic Acid as an Anchoring Group Article de journal S Panagiotakis; E Giannoudis; A Charisiadis; R Paravatou; M -E Lazaridi; M Kandyli; K Ladomenou; P A Angaridis; H C Bertrand; G D Sharma; A G Coutsolelos European Journal of Inorganic Chemistry, 2018 (20), p. 2369–2379, 2018. @article{Panagiotakis:2018, title = {Increased Efficiency of Dye-Sensitized Solar Cells by Incorporation of a π Spacer in Donor\textendashAcceptor Zinc Porphyrins Bearing Cyanoacrylic Acid as an Anchoring Group}, author = {S Panagiotakis and E Giannoudis and A Charisiadis and R Paravatou and M -E Lazaridi and M Kandyli and K Ladomenou and P A Angaridis and H C Bertrand and G D Sharma and A G Coutsolelos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044864237&doi=10.1002%2fejic.201800123&partnerID=40&md5=1a3cfeb98ec9917efc3f7e5dbcd02977}, doi = {10.1002/ejic.201800123}, year = {2018}, date = {2018-01-01}, journal = {European Journal of Inorganic Chemistry}, volume = {2018}, number = {20}, pages = {2369--2379}, abstract = {Two novel porphyrins, ZnP(SP)CNCOOH and ZnPCNCOOH, bearing cyanoacrylic acid as an anchoring group were synthesized. Porphyrin ZnP(SP)CNCOOH contains a π-conjugated spacer (SP) for improved electronic communication between the dye and the TiO2 electrode. The spacer bears polyethylene glycol chains to prevent dye aggregation and to enhance solubility of the dye. Electrochemical measurements and theoretical calculations suggest that both porphyrins are promising sensitizers for dye-sensitized solar cells (DSSCs), as their molecular orbital energy levels favor electron injection and dye regeneration. Solar cells sensitized by ZnP(SP)CNCOOH and ZnPCNCOOH show power conversion efficiencies of 7.61 and 5.02 %, respectively. Photovoltaic measurements (J\textendashV curves and incident photon to current conversion efficiency spectra) show that higher short-circuit current (Jsc) and open-circuit voltage (Voc) values are reached for the solar cell based on ZnP(SP)CNCOOH. This can be mainly ascribed to suppressed charge recombination, as indicated by their electrochemical impedance spectra. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Two novel porphyrins, ZnP(SP)CNCOOH and ZnPCNCOOH, bearing cyanoacrylic acid as an anchoring group were synthesized. Porphyrin ZnP(SP)CNCOOH contains a π-conjugated spacer (SP) for improved electronic communication between the dye and the TiO2 electrode. The spacer bears polyethylene glycol chains to prevent dye aggregation and to enhance solubility of the dye. Electrochemical measurements and theoretical calculations suggest that both porphyrins are promising sensitizers for dye-sensitized solar cells (DSSCs), as their molecular orbital energy levels favor electron injection and dye regeneration. Solar cells sensitized by ZnP(SP)CNCOOH and ZnPCNCOOH show power conversion efficiencies of 7.61 and 5.02 %, respectively. Photovoltaic measurements (J–V curves and incident photon to current conversion efficiency spectra) show that higher short-circuit current (Jsc) and open-circuit voltage (Voc) values are reached for the solar cell based on ZnP(SP)CNCOOH. This can be mainly ascribed to suppressed charge recombination, as indicated by their electrochemical impedance spectra. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
Nerves, H2O2 and Shh: Three players in the game of regeneration Article de journal Francesca Meda; Christine Rampon; Edmond Dupont; Carole Gauron; Aurélien Mourton; Isabelle Queguiner; Marion Thauvin; Michel Volovitch; Alain Joliot; Sophie Vriz Seminars in Cell & Developmental Biology, 80 , p. 65–73, 2018, ISSN: 1084-9521. @article{meda_nerves_2018, title = {Nerves, H2O2 and Shh: Three players in the game of regeneration}, author = {Francesca Meda and Christine Rampon and Edmond Dupont and Carole Gauron and Aur\'{e}lien Mourton and Isabelle Queguiner and Marion Thauvin and Michel Volovitch and Alain Joliot and Sophie Vriz}, url = {https://www.sciencedirect.com/science/article/pii/S1084952117304482}, doi = {10.1016/j.semcdb.2017.08.015}, issn = {1084-9521}, year = {2018}, date = {2018-01-01}, urldate = {2023-10-31}, journal = {Seminars in Cell & Developmental Biology}, volume = {80}, pages = {65--73}, series = {Redox signalling in development and regeneration}, abstract = {The tight control of reactive oxygen species (ROS) levels is required during regeneration. H2O2 in particular assumes clear signalling functions at different steps in this process. Injured nerves induce high levels of H2O2 through the activation of the Hedgehog (Shh) pathway, providing an environment that promotes cell plasticity, progenitor recruitment and blastema formation. In turn, high H2O2 levels contribute to growing axon attraction. Once re-innervation is completed, nerves subsequently downregulate H2O2 levels to their original state. A similar regulatory loop between H2O2 levels and nerves also exists during development. This suggests that redox signalling is a major actor in cell plasticity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The tight control of reactive oxygen species (ROS) levels is required during regeneration. H2O2 in particular assumes clear signalling functions at different steps in this process. Injured nerves induce high levels of H2O2 through the activation of the Hedgehog (Shh) pathway, providing an environment that promotes cell plasticity, progenitor recruitment and blastema formation. In turn, high H2O2 levels contribute to growing axon attraction. Once re-innervation is completed, nerves subsequently downregulate H2O2 levels to their original state. A similar regulatory loop between H2O2 levels and nerves also exists during development. This suggests that redox signalling is a major actor in cell plasticity. |
Ferrocifens labelled with an infrared rhenium tricarbonyl tag: Synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells Article de journal Y Wang; F Heinemann; S Top; A Dazzi; C Policar; L Henry; F Lambert; G Jaouen; M Salmain; A Vessieres Dalton Transactions, 47 (29), p. 9824–9833, 2018. @article{Wang:2018c, title = {Ferrocifens labelled with an infrared rhenium tricarbonyl tag: Synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells}, author = {Y Wang and F Heinemann and S Top and A Dazzi and C Policar and L Henry and F Lambert and G Jaouen and M Salmain and A Vessieres}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050854664&doi=10.1039%2fc8dt01582a&partnerID=40&md5=1eb695f8b77ceadad719c5ab75b11480}, doi = {10.1039/c8dt01582a}, year = {2018}, date = {2018-01-01}, journal = {Dalton Transactions}, volume = {47}, number = {29}, pages = {9824--9833}, abstract = {Antiproliferative activities of several members of the ferrocifen family, both in vitro and in vivo, are well documented although their precise location in cancer cells has not yet been elucidated. However, two different infrared imaging techniques have been used to map the non-cytotoxic cyrhetrenyl analogue of ferrociphenol in a single cell. This observation prompted us to tag two ferrocifens with a cyrhetrenyl unit [CpRe(CO)3; Cp = η5-cyclopentadienyl] by grafting it, via an ester bond, either to one of the phenols (4, 5) or to the hydroxypropyl chain (6). Complexes 4-6 retained a high cytotoxicity on breast cancer cells (MDA-MB-231) with IC50 values in the range 0.32-2.5 μM. Transmission IR spectroscopy was used to quantify the amount of cyrhetrenyl tag present in cells incubated with 5 or 6. The results show that after a 1-hour incubation of cells at 37 °C, complexes 5 and 6 are mainly present within cells while only a limited percentage, quantified by ICP-OES, remained in the incubation medium. AFM-IR spectroscopy, a technique coupling infrared irradiation with near-field AFM detection, was used to map the cyrhetrenyl unit in a single MDA-MB-231 cell, incubated at 37 °C for 1 hour with 10 μM of 6. The results show that signal distribution of the characteristic band of the Re(CO)3 entity at 1950 cm-1 matched those of amide and phosphate, thus indicating a location of the complex mainly in the cell nucleus. © 2018 The Royal Society of Chemistry.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Antiproliferative activities of several members of the ferrocifen family, both in vitro and in vivo, are well documented although their precise location in cancer cells has not yet been elucidated. However, two different infrared imaging techniques have been used to map the non-cytotoxic cyrhetrenyl analogue of ferrociphenol in a single cell. This observation prompted us to tag two ferrocifens with a cyrhetrenyl unit [CpRe(CO)3; Cp = η5-cyclopentadienyl] by grafting it, via an ester bond, either to one of the phenols (4, 5) or to the hydroxypropyl chain (6). Complexes 4-6 retained a high cytotoxicity on breast cancer cells (MDA-MB-231) with IC50 values in the range 0.32-2.5 μM. Transmission IR spectroscopy was used to quantify the amount of cyrhetrenyl tag present in cells incubated with 5 or 6. The results show that after a 1-hour incubation of cells at 37 °C, complexes 5 and 6 are mainly present within cells while only a limited percentage, quantified by ICP-OES, remained in the incubation medium. AFM-IR spectroscopy, a technique coupling infrared irradiation with near-field AFM detection, was used to map the cyrhetrenyl unit in a single MDA-MB-231 cell, incubated at 37 °C for 1 hour with 10 μM of 6. The results show that signal distribution of the characteristic band of the Re(CO)3 entity at 1950 cm-1 matched those of amide and phosphate, thus indicating a location of the complex mainly in the cell nucleus. © 2018 The Royal Society of Chemistry. |
2017 |
Direct Keap1-Nrf2 disruption as a potential therapeutic target for Alzheimer's disease Article de journal Fiona Kerr; Oyinkan Sofola-Adesakin; Dobril K Ivanov; Jemma Gatliff; Beatriz Gomez Perez-Nievas; Hélène C Bertrand; Pedro Martinez; Rebecca Callard; Inge Snoeren; Helena M Cochemé; Jennifer Adcott; Mobina Khericha; Jorge Iván Castillo-Quan; Geoffrey Wells; Wendy Noble; Janet Thornton; Linda Partridge PLOS Genetics, 13 (3), p. e1006593, 2017. @article{Kerr2017, title = {Direct Keap1-Nrf2 disruption as a potential therapeutic target for Alzheimer's disease}, author = {Fiona Kerr and Oyinkan Sofola-Adesakin and Dobril K Ivanov and Jemma Gatliff and Beatriz {Gomez Perez-Nievas} and H\'{e}l{\`{e}}ne C Bertrand and Pedro Martinez and Rebecca Callard and Inge Snoeren and Helena M Cochem\'{e} and Jennifer Adcott and Mobina Khericha and Jorge Iv\'{a}n Castillo-Quan and Geoffrey Wells and Wendy Noble and Janet Thornton and Linda Partridge}, url = {https://doi.org/10.1371/journal.pgen.1006593}, year = {2017}, date = {2017-03-01}, journal = {PLOS Genetics}, volume = {13}, number = {3}, pages = {e1006593}, publisher = {Public Library of Science}, abstract = {Author summary As our population ages the incidence of neurodegenerative diseases, including Alzheimer's disease (AD), is predicted to increase dramatically. Despite providing important symptomatic relief, existing treatments for such conditions do not slow-down disease progression, and this will cause an overwhelming future burden on our healthcare system and immense suffering for many more patients and their families. Nrf2 is a gene that normally protects cells from stressful conditions. Although we don't know why, Nrf2 is reduced in the brains of AD patients and this may explain the increased susceptibility of neurons to damage in neurodegenerative diseases. Our research, using a fruit fly model, identifies Keap1, a negative regulator of Nrf2, as a valid target for the rescue of AD-related Nrf2 defects and the subsequent prevention of neuronal degeneration. Moreover, we show that a new compound, which directly blocks the binding between Nrf2 and Keap1, can prevent toxicity of the AD-initiating A$beta$ peptide in mouse neurons. Hence, our study provides strong evidence that direct Keap1-Nrf2 disruptors can specifically target the defects in Nrf2 activity observed in neurodegenerative diseases, and supports the further development of such compounds as potential new drugs to prevent neuronal decline AD and other neurodegenerative conditions.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Author summary As our population ages the incidence of neurodegenerative diseases, including Alzheimer's disease (AD), is predicted to increase dramatically. Despite providing important symptomatic relief, existing treatments for such conditions do not slow-down disease progression, and this will cause an overwhelming future burden on our healthcare system and immense suffering for many more patients and their families. Nrf2 is a gene that normally protects cells from stressful conditions. Although we don't know why, Nrf2 is reduced in the brains of AD patients and this may explain the increased susceptibility of neurons to damage in neurodegenerative diseases. Our research, using a fruit fly model, identifies Keap1, a negative regulator of Nrf2, as a valid target for the rescue of AD-related Nrf2 defects and the subsequent prevention of neuronal degeneration. Moreover, we show that a new compound, which directly blocks the binding between Nrf2 and Keap1, can prevent toxicity of the AD-initiating A$beta$ peptide in mouse neurons. Hence, our study provides strong evidence that direct Keap1-Nrf2 disruptors can specifically target the defects in Nrf2 activity observed in neurodegenerative diseases, and supports the further development of such compounds as potential new drugs to prevent neuronal decline AD and other neurodegenerative conditions. |