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))
2024 |
Piezoelectric and microfluidic tuning of an infrared cavity for vibrational polariton studies Article de journal Wei Wang; Jaime de la Fuente Diez; Nicolas Delsuc; Juan Peng; Riccardo Spezia; Rodolphe Vuilleumier; Yong Chen Lab Chip, p. -, 2024. @article{D3LC01101A, title = {Piezoelectric and microfluidic tuning of an infrared cavity for vibrational polariton studies}, author = {Wei Wang and Jaime de la Fuente Diez and Nicolas Delsuc and Juan Peng and Riccardo Spezia and Rodolphe Vuilleumier and Yong Chen}, url = {http://dx.doi.org/10.1039/D3LC01101A}, doi = {10.1039/D3LC01101A}, year = {2024}, date = {2024-01-01}, journal = {Lab Chip}, pages = {-}, publisher = {The Royal Society of Chemistry}, abstract = {We developed a microfluidic system for vibrational polariton studies, which consists of two microfluidic chips: one for solution mixing and another for tuning an infrared cavity made of a pair of gold mirrors and a PDMS (polydimethylsiloxane) spacer. We show that the cavity of the system can be accurately tuned with either piezoelectric actuators or microflow-induced pressure to result in resonant coupling between a cavity mode and a variational mode of the solution molecules. Acrylonitrile solutions were chosen to prove the concept of vabriational strong coupling (VSC) of a CN stretching mode with light inside the cavity. We also show that the Rabi splitting energy is linearly proportional to the square root of molecular concentration, thereby proving the relevance and reliability of the system for VSC studies.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We developed a microfluidic system for vibrational polariton studies, which consists of two microfluidic chips: one for solution mixing and another for tuning an infrared cavity made of a pair of gold mirrors and a PDMS (polydimethylsiloxane) spacer. We show that the cavity of the system can be accurately tuned with either piezoelectric actuators or microflow-induced pressure to result in resonant coupling between a cavity mode and a variational mode of the solution molecules. Acrylonitrile solutions were chosen to prove the concept of vabriational strong coupling (VSC) of a CN stretching mode with light inside the cavity. We also show that the Rabi splitting energy is linearly proportional to the square root of molecular concentration, thereby proving the relevance and reliability of the system for VSC studies. |
Clotilde Policar; Nicolas Delsuc; Hél`ene Charlotte Bertrand Comptes Rendus. Chimie, 2024, (Online first). @article{CRCHIM_2024__27_S2_A12_0, title = {Metal complexes in cells: from design of catalytic antioxidants to imaging metal ions and designing metal-based probes in X-ray fluorescence and IR-imaging, a multidisciplinary collaborative journey in bioinorganic chemistry and inorganic chemical biology}, author = {Clotilde Policar and Nicolas Delsuc and H\'{e}l`ene Charlotte Bertrand}, doi = {10.5802/crchim.295}, year = {2024}, date = {2024-01-01}, journal = {Comptes Rendus. Chimie}, publisher = {Acad\'{e}mie des sciences, Paris}, note = {Online first}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
2023 |
Ruthenium(II) polypyridyl complexes as emerging photosensitisers for antibacterial photodynamic therapy Article de journal Ng Xiao Ying; Fong Kar Wai; Kiew Lik Voon; Katrina Chung Pooi Yin; Liew Yun Khoon; Nicolas Delsuc; Mohd Zulkefeli; Low May Lee Journal of Inorganic Biochemistry, p. 112425, 2023, ISSN: 0162-0134. @article{YING2023112425, title = {Ruthenium(II) polypyridyl complexes as emerging photosensitisers for antibacterial photodynamic therapy}, author = {Ng Xiao Ying and Fong Kar Wai and Kiew Lik Voon and Katrina Chung Pooi Yin and Liew Yun Khoon and Nicolas Delsuc and Mohd Zulkefeli and Low May Lee}, url = {https://www.sciencedirect.com/science/article/pii/S0162013423003070}, doi = {https://doi.org/10.1016/j.jinorgbio.2023.112425}, issn = {0162-0134}, year = {2023}, date = {2023-01-01}, journal = {Journal of Inorganic Biochemistry}, pages = {112425}, abstract = {Photodynamic therapy (PDT) has recently emerged as a potential valuable alternative to treat microbial infections. In PDT, singlet oxygen is generated in the presence of photosensitisers and oxygen under light irradiation of a specific wavelength, causing cytotoxic damage to bacteria. This review highlights different generations of photosensitisers and the common characteristics of ideal photosensitisers. It also focuses on the emergence of ruthenium and more specifically on Ru(II) polypyridyl complexes as metal-based photosensitisers used in antimicrobial photodynamic therapy (aPDT). Their photochemical and photophysical properties as well as structures are discussed while relating them to their phototoxicity. The use of Ru(II) complexes with recent advancements such as nanoformulations, combinatory therapy and photothermal therapy to improve on previous shortcomings of the complexes are outlined. Future perspectives of these complexes used in two-photon PDT, photoacoustic imaging and sonotherapy are also discussed. This review covers the literature published from 2017 to 2023.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Photodynamic therapy (PDT) has recently emerged as a potential valuable alternative to treat microbial infections. In PDT, singlet oxygen is generated in the presence of photosensitisers and oxygen under light irradiation of a specific wavelength, causing cytotoxic damage to bacteria. This review highlights different generations of photosensitisers and the common characteristics of ideal photosensitisers. It also focuses on the emergence of ruthenium and more specifically on Ru(II) polypyridyl complexes as metal-based photosensitisers used in antimicrobial photodynamic therapy (aPDT). Their photochemical and photophysical properties as well as structures are discussed while relating them to their phototoxicity. The use of Ru(II) complexes with recent advancements such as nanoformulations, combinatory therapy and photothermal therapy to improve on previous shortcomings of the complexes are outlined. Future perspectives of these complexes used in two-photon PDT, photoacoustic imaging and sonotherapy are also discussed. This review covers the literature published from 2017 to 2023. |
TMED10 mediates the loading of neosynthesised Sonic Hedgehog in COPII vesicles for efficient secretion and signalling Article de journal Yonis Bare; Tamás Matusek; Sophie Vriz; Maika S Deffieu; Pascal P Thérond; Raphael Gaudin Cellular and molecular life sciences: CMLS, 80 (9), p. 266, 2023, ISSN: 1420-9071. @article{bare_tmed10_2023, title = {TMED10 mediates the loading of neosynthesised Sonic Hedgehog in COPII vesicles for efficient secretion and signalling}, author = {Yonis Bare and Tam\'{a}s Matusek and Sophie Vriz and Maika S Deffieu and Pascal P Th\'{e}rond and Raphael Gaudin}, doi = {10.1007/s00018-023-04918-1}, issn = {1420-9071}, year = {2023}, date = {2023-01-01}, journal = {Cellular and molecular life sciences: CMLS}, volume = {80}, number = {9}, pages = {266}, abstract = {The morphogen Sonic Hedgehog (SHH) plays an important role in coordinating embryonic development. Short- and long-range SHH signalling occurs through a variety of membrane-associated and membrane-free forms. However, the molecular mechanisms that govern the early events of the trafficking of neosynthesised SHH in mammalian cells are still poorly understood. Here, we employed the retention using selective hooks (RUSH) system to show that newly-synthesised SHH is trafficked through the classical biosynthetic secretory pathway, using TMED10 as an endoplasmic reticulum (ER) cargo receptor for efficient ER-to-Golgi transport and Rab6 vesicles for Golgi-to-cell surface trafficking. TMED10 and SHH colocalized at ER exit sites (ERES), and TMED10 depletion significantly delays SHH loading onto ERES and subsequent exit leading to significant SHH release defects. Finally, we utilised the Drosophila wing imaginal disc model to demonstrate that the homologue of TMED10, Baiser (Bai), participates in Hedgehog (Hh) secretion and signalling in vivo. In conclusion, our work highlights the role of TMED10 in cargo-specific egress from the ER and sheds light on novel important partners of neosynthesised SHH secretion with potential impact on embryonic development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The morphogen Sonic Hedgehog (SHH) plays an important role in coordinating embryonic development. Short- and long-range SHH signalling occurs through a variety of membrane-associated and membrane-free forms. However, the molecular mechanisms that govern the early events of the trafficking of neosynthesised SHH in mammalian cells are still poorly understood. Here, we employed the retention using selective hooks (RUSH) system to show that newly-synthesised SHH is trafficked through the classical biosynthetic secretory pathway, using TMED10 as an endoplasmic reticulum (ER) cargo receptor for efficient ER-to-Golgi transport and Rab6 vesicles for Golgi-to-cell surface trafficking. TMED10 and SHH colocalized at ER exit sites (ERES), and TMED10 depletion significantly delays SHH loading onto ERES and subsequent exit leading to significant SHH release defects. Finally, we utilised the Drosophila wing imaginal disc model to demonstrate that the homologue of TMED10, Baiser (Bai), participates in Hedgehog (Hh) secretion and signalling in vivo. In conclusion, our work highlights the role of TMED10 in cargo-specific egress from the ER and sheds light on novel important partners of neosynthesised SHH secretion with potential impact on embryonic development. |
Hydrogen Peroxide Signaling in Physiology and Pathology Article de journal Christine Rampon; Sophie Vriz Antioxidants, 12 (3), p. 661, 2023, ISSN: 2076-3921, (Number: 3 Publisher: Multidisciplinary Digital Publishing Institute). @article{rampon_hydrogen_2023, title = {Hydrogen Peroxide Signaling in Physiology and Pathology}, author = {Christine Rampon and Sophie Vriz}, url = {https://www.mdpi.com/2076-3921/12/3/661}, doi = {10.3390/antiox12030661}, issn = {2076-3921}, year = {2023}, date = {2023-01-01}, urldate = {2023-10-31}, journal = {Antioxidants}, volume = {12}, number = {3}, pages = {661}, abstract = {Reactive oxygen species (ROS) were originally described as toxic by-products of aerobic cellular energy metabolism associated with the development of several diseases, such as cancer, neurodegenerative diseases, and diabetes [...]}, note = {Number: 3 Publisher: Multidisciplinary Digital Publishing Institute}, keywords = {}, pubstate = {published}, tppubtype = {article} } Reactive oxygen species (ROS) were originally described as toxic by-products of aerobic cellular energy metabolism associated with the development of several diseases, such as cancer, neurodegenerative diseases, and diabetes [...] |
2022 |
An early Shh-H2O2 reciprocal regulatory interaction controls the regenerative program during zebrafish fin regeneration Article de journal Marion Thauvin; Rodolphe Matias de Sousa; Marine Alves; Michel Volovitch; Sophie Vriz; Christine Rampon Journal of Cell Science, 135 (6), p. jcs259664, 2022, ISSN: 1477-9137. @article{thauvin_early_2022, title = {An early Shh-H2O2 reciprocal regulatory interaction controls the regenerative program during zebrafish fin regeneration}, author = {Marion Thauvin and Rodolphe Matias de Sousa and Marine Alves and Michel Volovitch and Sophie Vriz and Christine Rampon}, doi = {10.1242/jcs.259664}, issn = {1477-9137}, year = {2022}, date = {2022-01-01}, journal = {Journal of Cell Science}, volume = {135}, number = {6}, pages = {jcs259664}, abstract = {Reactive oxygen species (ROS), originally classified as toxic molecules, have attracted increasing interest given their actions in cell signaling. Hydrogen peroxide (H2O2), the major ROS produced by cells, acts as a second messenger to modify redox-sensitive proteins or lipids. After caudal fin amputation, tight spatiotemporal regulation of ROS is required first for wound healing and later to initiate the regenerative program. However, the mechanisms carrying out this sustained ROS production and their integration with signaling pathways remain poorly understood. We focused on the early dialog between H2O2 and Sonic hedgehog (Shh) during zebrafish fin regeneration. We demonstrate that H2O2 controls Shh expression and that Shh in turn regulates the H2O2 level via a canonical pathway. Moreover, the means of this tight reciprocal control change during the successive phases of the regenerative program. Dysregulation of the Hedgehog pathway has been implicated in several developmental syndromes, diabetes and cancer. These data support the existence of an early positive crosstalk between Shh and H2O2 that might be more generally involved in various processes paving the way to improve regenerative processes, particularly in vertebrates.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Reactive oxygen species (ROS), originally classified as toxic molecules, have attracted increasing interest given their actions in cell signaling. Hydrogen peroxide (H2O2), the major ROS produced by cells, acts as a second messenger to modify redox-sensitive proteins or lipids. After caudal fin amputation, tight spatiotemporal regulation of ROS is required first for wound healing and later to initiate the regenerative program. However, the mechanisms carrying out this sustained ROS production and their integration with signaling pathways remain poorly understood. We focused on the early dialog between H2O2 and Sonic hedgehog (Shh) during zebrafish fin regeneration. We demonstrate that H2O2 controls Shh expression and that Shh in turn regulates the H2O2 level via a canonical pathway. Moreover, the means of this tight reciprocal control change during the successive phases of the regenerative program. Dysregulation of the Hedgehog pathway has been implicated in several developmental syndromes, diabetes and cancer. These data support the existence of an early positive crosstalk between Shh and H2O2 that might be more generally involved in various processes paving the way to improve regenerative processes, particularly in vertebrates. |
Assessment of iron nanoparticle distribution in mouse models using ultrashort-echo-time MRI Article de journal Andreas Boss; Laura Heeb; Divya Vats; Fabian H L Starsich; Alice Balfourier; Inge K Herrmann; Anurag Gupta NMR in Biomedicine, p. e4690, 2022, ISSN: 1099-1492. @article{boss_assessment_nodate, title = {Assessment of iron nanoparticle distribution in mouse models using ultrashort-echo-time MRI}, author = {Andreas Boss and Laura Heeb and Divya Vats and Fabian H L Starsich and Alice Balfourier and Inge K Herrmann and Anurag Gupta}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/nbm.4690}, doi = {10.1002/nbm.4690}, issn = {1099-1492}, year = {2022}, date = {2022-01-01}, urldate = {2022-04-21}, journal = {NMR in Biomedicine}, pages = {e4690}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Alice Balfourier; Elena Tsolaki; Laura Heeb; Fabian HL Starsich; Daniel Klose; Andreas Boss; Anurag Gupta; Alexander Gogos; Inge K Herrmann Small Methods, p. 2201061, 2022. @article{balfourier2022multiscale, title = {Multiscale Multimodal Investigation of the Intratissural Biodistribution of Iron Nanotherapeutics with Single Cell Resolution Reveals Co-Localization with Endogenous Iron in Splenic Macrophages}, author = {Alice Balfourier and Elena Tsolaki and Laura Heeb and Fabian HL Starsich and Daniel Klose and Andreas Boss and Anurag Gupta and Alexander Gogos and Inge K Herrmann}, doi = {10.1002/smtd.202201061}, year = {2022}, date = {2022-01-01}, journal = {Small Methods}, pages = {2201061}, publisher = {Wiley Online Library}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Importance of Metal Biotransformation in Cell Response to Metallic Nanoparticles: A Transcriptomic Meta-analysis Study Article de journal Alice Balfourier; Anne-Pia Marty; Florence Gazeau ACS Nanoscience Au, p. acsnanoscienceau.2c00035, 2022, ISSN: 2694-2496, 2694-2496. @article{balfourier_importance_2022, title = {Importance of Metal Biotransformation in Cell Response to Metallic Nanoparticles: A Transcriptomic Meta-analysis Study}, author = {Alice Balfourier and Anne-Pia Marty and Florence Gazeau}, doi = {10.1021/acsnanoscienceau.2c00035}, issn = {2694-2496, 2694-2496}, year = {2022}, date = {2022-01-01}, urldate = {2023-01-06}, journal = {ACS Nanoscience Au}, pages = {acsnanoscienceau.2c00035}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Fate and biological impact of persistent luminescence nanoparticles after injection in mice: a one-year follow-up Article de journal Thomas Lécuyer; Johanne Seguin; Alice Balfourier; Marine Delagrange; Pierre Burckel; René Lai-Kuen; Virginie Mignon; Bertrand Ducos; Michael Tharaud; Bruno Saubaméa; Daniel Scherman; Nathalie Mignet; Florence Gazeau; Cyrille Richard Nanoscale, p. 10.1039.D2NR03546D, 2022, ISSN: 2040-3364, 2040-3372. @article{lecuyer_fate_2022, title = {Fate and biological impact of persistent luminescence nanoparticles after injection in mice: a one-year follow-up}, author = {Thomas L\'{e}cuyer and Johanne Seguin and Alice Balfourier and Marine Delagrange and Pierre Burckel and Ren\'{e} Lai-Kuen and Virginie Mignon and Bertrand Ducos and Michael Tharaud and Bruno Saubam\'{e}a and Daniel Scherman and Nathalie Mignet and Florence Gazeau and Cyrille Richard}, doi = {10.1039/D2NR03546D}, issn = {2040-3364, 2040-3372}, year = {2022}, date = {2022-01-01}, urldate = {2022-10-17}, journal = {Nanoscale}, pages = {10.1039.D2NR03546D}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Improvement of Peptidyl Copper Complexes Mimicking Catalase: A Subtle Balance between Thermodynamic Stability and Resistance towards H2O2 Degradation Article de journal Yaqine Ben Hadj Hammouda; Koudedja Coulibaly; Alimatou Bathily; Magdalene Teoh Sook Han; Clotilde Policar; Nicolas Delsuc Molecules, 27 (17), 2022, ISSN: 1420-3049. @article{molecules27175476, title = {Improvement of Peptidyl Copper Complexes Mimicking Catalase: A Subtle Balance between Thermodynamic Stability and Resistance towards H2O2 Degradation}, author = {Yaqine Ben Hadj Hammouda and Koudedja Coulibaly and Alimatou Bathily and Magdalene Teoh Sook Han and Clotilde Policar and Nicolas Delsuc}, url = {https://www.mdpi.com/1420-3049/27/17/5476}, doi = {10.3390/molecules27175476}, issn = {1420-3049}, year = {2022}, date = {2022-01-01}, journal = {Molecules}, volume = {27}, number = {17}, abstract = {Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H2O2 concentration by catalyzing its dismutation. H2O2 is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H2O2 by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H2O2 dismutation, their thermodynamic stability and their resistance to H2O2 degradation are very different, with (CATm2)Cu2 being the most promising catalyst.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H2O2 concentration by catalyzing its dismutation. H2O2 is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H2O2 by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H2O2 dismutation, their thermodynamic stability and their resistance to H2O2 degradation are very different, with (CATm2)Cu2 being the most promising catalyst. |
Deciphering the Metal Speciation in Low-Molecular-Weight Complexes by IMS-MS: Application to the Detection of Manganese Superoxide Dismutase Mimics in Cell Lysates Article de journal Martha Zoumpoulaki; Gabrielle Schanne; Nicolas Delsuc; Hugues Preud'homme; Elodie Quévrain; Nicolas Eskenazi; Géraldine Gazzah; Regis Guillot; Philippe Seksik; Joelle Vinh; Ryszard Lobinski; Clotilde Policar Angewandte Chemie International Edition, n/a (n/a), p. e202203066, 2022. @article{https://doi.org/10.1002/anie.202203066, title = {Deciphering the Metal Speciation in Low-Molecular-Weight Complexes by IMS-MS: Application to the Detection of Manganese Superoxide Dismutase Mimics in Cell Lysates}, author = {Martha Zoumpoulaki and Gabrielle Schanne and Nicolas Delsuc and Hugues Preud'homme and Elodie Qu\'{e}vrain and Nicolas Eskenazi and G\'{e}raldine Gazzah and Regis Guillot and Philippe Seksik and Joelle Vinh and Ryszard Lobinski and Clotilde Policar}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202203066}, doi = {https://doi.org/10.1002/anie.202203066}, year = {2022}, date = {2022-01-01}, journal = {Angewandte Chemie International Edition}, volume = {n/a}, number = {n/a}, pages = {e202203066}, abstract = {Abstract The detection and quantification of exogenous metal complexes are crucial to understanding their activity in intricate biological media. MnII complexes are difficult to detect and quantify because of low association constants, and high lability. The superoxide dismutase (SOD) mimic (or mimetic) labelled Mn1 is based on a 1,2-di-aminoethane functionalized with imidazole and phenolate and has good intrinsic anti-superoxide, antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-activated intestinal epithelial HT29-MD2 cells, similar to that of its propylated analogue labelled Mn1P. Ion mobility spectrometry-mass spectrometry (IMS-MS) is a powerful technique for separating low molecular weight (LMW) metal complexes and can even separate complexes with the same ligand but bound to different divalent metal cations with similar ionic radii. We demonstrated the intracellular presence of the Mn1 and Mn1P complexes, at least partly intact, in lysates of cells incubated with the complexes and estimated the intracellular Mn1P concentration using a Co-13C6 analogue.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract The detection and quantification of exogenous metal complexes are crucial to understanding their activity in intricate biological media. MnII complexes are difficult to detect and quantify because of low association constants, and high lability. The superoxide dismutase (SOD) mimic (or mimetic) labelled Mn1 is based on a 1,2-di-aminoethane functionalized with imidazole and phenolate and has good intrinsic anti-superoxide, antioxidant and anti-inflammatory activities in lipopolysaccharide (LPS)-activated intestinal epithelial HT29-MD2 cells, similar to that of its propylated analogue labelled Mn1P. Ion mobility spectrometry-mass spectrometry (IMS-MS) is a powerful technique for separating low molecular weight (LMW) metal complexes and can even separate complexes with the same ligand but bound to different divalent metal cations with similar ionic radii. We demonstrated the intracellular presence of the Mn1 and Mn1P complexes, at least partly intact, in lysates of cells incubated with the complexes and estimated the intracellular Mn1P concentration using a Co-13C6 analogue. |
Inertness of Superoxide Dismutase Mimics Mn(II) Complexes Based on an Open-Chain Ligand, Bioactivity, and Detection in Intestinal Epithelial Cells Article de journal Gabrielle Schanne; Martha Zoumpoulaki; Géraldine Gazzah; Amandine Vincent; Hugues Preud’homme; Ryszard Lobinski; Sylvie Demignot; Philippe Seksik; Nicolas Delsuc; Clotilde Policar Oxidative Medicine and Cellular Longevity, 2022 , p. e3858122, 2022, ISSN: 1942-0900, (Publisher: Hindawi). @article{schanne_inertness_2022, title = {Inertness of Superoxide Dismutase Mimics Mn(II) Complexes Based on an Open-Chain Ligand, Bioactivity, and Detection in Intestinal Epithelial Cells}, author = {Gabrielle Schanne and Martha Zoumpoulaki and G\'{e}raldine Gazzah and Amandine Vincent and Hugues Preud’homme and Ryszard Lobinski and Sylvie Demignot and Philippe Seksik and Nicolas Delsuc and Clotilde Policar}, url = {https://www.hindawi.com/journals/omcl/2022/3858122/}, doi = {10.1155/2022/3858122}, issn = {1942-0900}, year = {2022}, date = {2022-01-01}, urldate = {2022-04-03}, journal = {Oxidative Medicine and Cellular Longevity}, volume = {2022}, pages = {e3858122}, abstract = {Oxidative stress is known to play a major role in the pathogenesis of inflammatory bowel diseases (IBDs), and, in particular, superoxide dismutase (SODs) defenses were shown to be weakened in patients suffering from IBDs. SOD mimics, also called SOD mimetics, as low-molecular-weight complexes reproducing the activity of SOD, constitute promising antioxidant catalytic metallodrugs in the context of IBDs. A Mn(II) complex SOD mimic (Mn1) based on an open-chain diaminoethane ligand exerting antioxidant and anti-inflammatory effects on an intestinal epithelial cellular model was shown to experience metal exchanges between the manganese center and metal ions present in the biological environment (such as Zn(II)) to some degrees. As the resulting complexes (mainly Zn(II)) were shown to be inactive, improving the kinetic inertness of Mn(II) complexes based on open-chain ligands is key to improve their bioactivity in a cellular context. We report here the study of three new Mn(II) complexes resulting from Mn1 functionalization with a cyclohexyl and/or a propyl group meant to limit, respectively, (a) metal exchanges and (b) deprotonation of an amine from the 1,2-diaminoethane central scaffold. The new manganese-based SOD mimics display a higher intrinsic SOD activity and also improved kinetic inertness in metal ion exchange processes (with Zn(II), Cu(II), Ni(II), and Co(II)). They were shown to provide anti-inflammatory and antioxidant effects in cells at lower doses than Mn1 (down to 10 μM). This improvement was due to their higher inertness against metal-assisted dissociation and not to different cellular overall accumulations. Based on its higher inertness, the SOD mimic containing both the propyl and the cyclohexyl moieties was suitable for intracellular detection and quantification by mass spectrometry, quantification, that was achieved by using a 13C-labeled Co-based analog of the SOD mimics as an external heavy standard.}, note = {Publisher: Hindawi}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress is known to play a major role in the pathogenesis of inflammatory bowel diseases (IBDs), and, in particular, superoxide dismutase (SODs) defenses were shown to be weakened in patients suffering from IBDs. SOD mimics, also called SOD mimetics, as low-molecular-weight complexes reproducing the activity of SOD, constitute promising antioxidant catalytic metallodrugs in the context of IBDs. A Mn(II) complex SOD mimic (Mn1) based on an open-chain diaminoethane ligand exerting antioxidant and anti-inflammatory effects on an intestinal epithelial cellular model was shown to experience metal exchanges between the manganese center and metal ions present in the biological environment (such as Zn(II)) to some degrees. As the resulting complexes (mainly Zn(II)) were shown to be inactive, improving the kinetic inertness of Mn(II) complexes based on open-chain ligands is key to improve their bioactivity in a cellular context. We report here the study of three new Mn(II) complexes resulting from Mn1 functionalization with a cyclohexyl and/or a propyl group meant to limit, respectively, (a) metal exchanges and (b) deprotonation of an amine from the 1,2-diaminoethane central scaffold. The new manganese-based SOD mimics display a higher intrinsic SOD activity and also improved kinetic inertness in metal ion exchange processes (with Zn(II), Cu(II), Ni(II), and Co(II)). They were shown to provide anti-inflammatory and antioxidant effects in cells at lower doses than Mn1 (down to 10 μM). This improvement was due to their higher inertness against metal-assisted dissociation and not to different cellular overall accumulations. Based on its higher inertness, the SOD mimic containing both the propyl and the cyclohexyl moieties was suitable for intracellular detection and quantification by mass spectrometry, quantification, that was achieved by using a 13C-labeled Co-based analog of the SOD mimics as an external heavy standard. |
Cellular Detection of a Mitochondria Targeted Brominated Vinyl Triphenylamine Optical Probe (TP−Br) by X-Ray Fluorescence Microscopy Article de journal Sounderya Nagarajan; Florent Poyer; Laura Fourmois; Delphine Naud-Martin; Kadda Medjoubi; Andrea Somogyi; Gabrielle Schanne; Lucas Henry; Nicolas Delsuc; Clotilde Policar; Helene C Bertrand; Florence Mahuteau-Betzer Chemistry – A European Journal, 28 (15), p. e202104424, 2022. @article{https://doi.org/10.1002/chem.202104424, title = {Cellular Detection of a Mitochondria Targeted Brominated Vinyl Triphenylamine Optical Probe (TP−Br) by X-Ray Fluorescence Microscopy}, author = {Sounderya Nagarajan and Florent Poyer and Laura Fourmois and Delphine Naud-Martin and Kadda Medjoubi and Andrea Somogyi and Gabrielle Schanne and Lucas Henry and Nicolas Delsuc and Clotilde Policar and Helene C Bertrand and Florence Mahuteau-Betzer}, url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202104424}, doi = {https://doi.org/10.1002/chem.202104424}, year = {2022}, date = {2022-01-01}, journal = {Chemistry \textendash A European Journal}, volume = {28}, number = {15}, pages = {e202104424}, abstract = {Abstract Triphenylamine (TP) derivatives such as two-branch cationic vinylbenzimidazolium triphenylamine TP−2Bzim are promising turn-on fluorescent probes suitable for two-photon imaging, labelling mitochondria in live cells. Here, we designed two TP−2Bzim derivatives as bimodal probes suitable for X-ray fluorescence imaging. The conjugation of the TP core with a rhenium tricarbonyl moiety in the TP−RePyta probe altered the localisation in live cells from mitochondria to lysosomes. The introduction of bromine on the TP core generated the TP−Br probe retaining good photophysical properties and mitochondria labelling in live cells. The influence of calcium channels in the uptake of TP−Br was studied. Synchrotron Radiation X-ray Fluorescence (SXRF) imaging of bromine enabled the detection of TP−Br and suggested a negligible presence of the probe in an unbound state in the incubated cells, a crucial point in the development of these probes. This study paves the way towards the development of TP probes as specific organelle stainers suitable for SXRF imaging.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Triphenylamine (TP) derivatives such as two-branch cationic vinylbenzimidazolium triphenylamine TP−2Bzim are promising turn-on fluorescent probes suitable for two-photon imaging, labelling mitochondria in live cells. Here, we designed two TP−2Bzim derivatives as bimodal probes suitable for X-ray fluorescence imaging. The conjugation of the TP core with a rhenium tricarbonyl moiety in the TP−RePyta probe altered the localisation in live cells from mitochondria to lysosomes. The introduction of bromine on the TP core generated the TP−Br probe retaining good photophysical properties and mitochondria labelling in live cells. The influence of calcium channels in the uptake of TP−Br was studied. Synchrotron Radiation X-ray Fluorescence (SXRF) imaging of bromine enabled the detection of TP−Br and suggested a negligible presence of the probe in an unbound state in the incubated cells, a crucial point in the development of these probes. This study paves the way towards the development of TP probes as specific organelle stainers suitable for SXRF imaging. |
SOD mimics: From the tool box of the chemists to cellular studies Article de journal Clotilde Policar; Jean Bouvet; Hélène C Bertrand; Nicolas Delsuc Current Opinion in Chemical Biology, 67 , p. 102109, 2022, ISSN: 1367-5931. @article{POLICAR2022102109, title = {SOD mimics: From the tool box of the chemists to cellular studies}, author = {Clotilde Policar and Jean Bouvet and H\'{e}l\`{e}ne C Bertrand and Nicolas Delsuc}, url = {https://www.sciencedirect.com/science/article/pii/S136759312100154X}, doi = {https://doi.org/10.1016/j.cbpa.2021.102109}, issn = {1367-5931}, year = {2022}, date = {2022-01-01}, journal = {Current Opinion in Chemical Biology}, volume = {67}, pages = {102109}, abstract = {Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2−) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Superoxide dismutases (SODs) are metalloproteins that protect cells against oxidative stress by controlling the concentration of superoxide (O2−) through catalysis of its dismutation. The activity of superoxide dismutases can be mimicked by low-molecular-weight complexes having potential therapeutic applications. This review presents recent strategies for designing efficient SOD mimics, from molecular metal complexes to nanomaterials. Studies of these systems in cells reveal that some SOD mimics, designed to react directly with superoxide, may also indirectly enhance the cellular antioxidant arsenal. Finally, a good understanding of the bioactivity requires information on the cell-penetration, speciation, and subcellular location of the SOD mimics: we will describe recent studies and new techniques that open opportunities for characterizing SOD mimics in biological environments. |
Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives Article de journal Alexander I Kostyuk; Maria-Armineh Tossounian; Anastasiya S Panova; Marion Thauvin; Roman I Raevskii; Daria Ezeriņa; Khadija Wahni; Inge Van Molle; Anastasia D Sergeeva; Didier Vertommen; Andrey Yu. Gorokhovatsky; Mikhail S Baranov; Sophie Vriz; Joris Messens; Dmitry S Bilan; Vsevolod V Belousov Nature Communications, 13 , p. 171, 2022, ISSN: 2041-1723. @article{kostyuk_hypocrates_2022, title = {Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives}, author = {Alexander I Kostyuk and Maria-Armineh Tossounian and Anastasiya S Panova and Marion Thauvin and Roman I Raevskii and Daria Ezeri\c{n}a and Khadija Wahni and Inge Van Molle and Anastasia D Sergeeva and Didier Vertommen and Andrey Yu. Gorokhovatsky and Mikhail S Baranov and Sophie Vriz and Joris Messens and Dmitry S Bilan and Vsevolod V Belousov}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748444/}, doi = {10.1038/s41467-021-27796-2}, issn = {2041-1723}, year = {2022}, date = {2022-01-01}, urldate = {2023-10-31}, journal = {Nature Communications}, volume = {13}, pages = {171}, abstract = {The lack of tools to monitor the dynamics of (pseudo)hypohalous acids in live cells and tissues hinders a better understanding of inflammatory processes. Here we present a fluorescent genetically encoded biosensor, Hypocrates, for the visualization of (pseudo)hypohalous acids and their derivatives. Hypocrates consists of a circularly permuted yellow fluorescent protein integrated into the structure of the transcription repressor NemR from Escherichia coli. We show that Hypocrates is ratiometric, reversible, and responds to its analytes in the 106 M−1s−1 range. Solving the Hypocrates X-ray structure provided insights into its sensing mechanism, allowing determination of the spatial organization in this circularly permuted fluorescent protein-based redox probe. We exemplify its applicability by imaging hypohalous stress in bacteria phagocytosed by primary neutrophils. Finally, we demonstrate that Hypocrates can be utilized in combination with HyPerRed for the simultaneous visualization of (pseudo)hypohalous acids and hydrogen peroxide dynamics in a zebrafish tail fin injury model., There are a lack of tools to study the dynamics of (pseudo)hypohalous acids in live cells. Here the authors report a genetically encoded fluorescent biosensor, Hypocrates, for (pseudo)hypohalous acids and their derivatives which they use in cells and in a zebrafish tail fin injury model.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The lack of tools to monitor the dynamics of (pseudo)hypohalous acids in live cells and tissues hinders a better understanding of inflammatory processes. Here we present a fluorescent genetically encoded biosensor, Hypocrates, for the visualization of (pseudo)hypohalous acids and their derivatives. Hypocrates consists of a circularly permuted yellow fluorescent protein integrated into the structure of the transcription repressor NemR from Escherichia coli. We show that Hypocrates is ratiometric, reversible, and responds to its analytes in the 106 M−1s−1 range. Solving the Hypocrates X-ray structure provided insights into its sensing mechanism, allowing determination of the spatial organization in this circularly permuted fluorescent protein-based redox probe. We exemplify its applicability by imaging hypohalous stress in bacteria phagocytosed by primary neutrophils. Finally, we demonstrate that Hypocrates can be utilized in combination with HyPerRed for the simultaneous visualization of (pseudo)hypohalous acids and hydrogen peroxide dynamics in a zebrafish tail fin injury model., There are a lack of tools to study the dynamics of (pseudo)hypohalous acids in live cells. Here the authors report a genetically encoded fluorescent biosensor, Hypocrates, for (pseudo)hypohalous acids and their derivatives which they use in cells and in a zebrafish tail fin injury model. |
Fgf8 dynamics and critical slowing down may account for the temperature independence of somitogenesis Article de journal Weiting Zhang; Pierluigi Scerbo; Marine Delagrange; Virginie Candat; Vanessa Mayr; Sophie Vriz; Martin Distel; Bertrand Ducos; David Bensimon Communications Biology, 5 (1), p. 1–10, 2022, ISSN: 2399-3642, (Number: 1 Publisher: Nature Publishing Group). @article{zhang_fgf8_2022, title = {Fgf8 dynamics and critical slowing down may account for the temperature independence of somitogenesis}, author = {Weiting Zhang and Pierluigi Scerbo and Marine Delagrange and Virginie Candat and Vanessa Mayr and Sophie Vriz and Martin Distel and Bertrand Ducos and David Bensimon}, url = {https://www.nature.com/articles/s42003-022-03053-0}, doi = {10.1038/s42003-022-03053-0}, issn = {2399-3642}, year = {2022}, date = {2022-01-01}, urldate = {2023-10-31}, journal = {Communications Biology}, volume = {5}, number = {1}, pages = {1--10}, abstract = {Somitogenesis, the segmentation of the antero-posterior axis in vertebrates, is thought to result from the interactions between a genetic oscillator and a posterior-moving determination wavefront. The segment (somite) size is set by the product of the oscillator period and the velocity of the determination wavefront. Surprisingly, while the segmentation period can vary by a factor three between 20 °C and 32 °C, the somite size is constant. How this temperature independence is achieved is a mystery that we address in this study. Using RT-qPCR we show that the endogenous fgf8 mRNA concentration decreases during somitogenesis and correlates with the exponent of the shrinking pre-somitic mesoderm (PSM) size. As the temperature decreases, the dynamics of fgf8 and many other gene transcripts, as well as the segmentation frequency and the PSM shortening and tail growth rates slows down as T\textendashTc (with Tc = 14.4 °C). This behavior characteristic of a system near a critical point may account for the temperature independence of somitogenesis in zebrafish.}, note = {Number: 1 Publisher: Nature Publishing Group}, keywords = {}, pubstate = {published}, tppubtype = {article} } Somitogenesis, the segmentation of the antero-posterior axis in vertebrates, is thought to result from the interactions between a genetic oscillator and a posterior-moving determination wavefront. The segment (somite) size is set by the product of the oscillator period and the velocity of the determination wavefront. Surprisingly, while the segmentation period can vary by a factor three between 20 °C and 32 °C, the somite size is constant. How this temperature independence is achieved is a mystery that we address in this study. Using RT-qPCR we show that the endogenous fgf8 mRNA concentration decreases during somitogenesis and correlates with the exponent of the shrinking pre-somitic mesoderm (PSM) size. As the temperature decreases, the dynamics of fgf8 and many other gene transcripts, as well as the segmentation frequency and the PSM shortening and tail growth rates slows down as T–Tc (with Tc = 14.4 °C). This behavior characteristic of a system near a critical point may account for the temperature independence of somitogenesis in zebrafish. |
Reciprocal Regulation of Shh Trafficking and H2O2 Levels via a Noncanonical BOC-Rac1 Pathway Article de journal Marion Thauvin; Irène Amblard; Christine Rampon; Aurélien Mourton; Isabelle Queguiner; Chenge Li; Arnaud Gautier; Alain Joliot; Michel Volovitch; Sophie Vriz Antioxidants (Basel, Switzerland), 11 (4), p. 718, 2022, ISSN: 2076-3921. @article{thauvin_reciprocal_2022, title = {Reciprocal Regulation of Shh Trafficking and H2O2 Levels via a Noncanonical BOC-Rac1 Pathway}, author = {Marion Thauvin and Ir\`{e}ne Amblard and Christine Rampon and Aur\'{e}lien Mourton and Isabelle Queguiner and Chenge Li and Arnaud Gautier and Alain Joliot and Michel Volovitch and Sophie Vriz}, doi = {10.3390/antiox11040718}, issn = {2076-3921}, year = {2022}, date = {2022-01-01}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {718}, abstract = {Among molecules that bridge environment, cell metabolism, and cell signaling, hydrogen peroxide (H2O2) recently appeared as an emerging but central player. Its level depends on cell metabolism and environment and was recently shown to play key roles during embryogenesis, contrasting with its long-established role in disease progression. We decided to explore whether the secreted morphogen Sonic hedgehog (Shh), known to be essential in a variety of biological processes ranging from embryonic development to adult tissue homeostasis and cancers, was part of these interactions. Here, we report that H2O2 levels control key steps of Shh delivery in cell culture: increased levels reduce primary secretion, stimulate endocytosis and accelerate delivery to recipient cells; in addition, physiological in vivo modulation of H2O2 levels changes Shh distribution and tissue patterning. Moreover, a feedback loop exists in which Shh trafficking controls H2O2 synthesis via a non-canonical BOC-Rac1 pathway, leading to cytoneme growth. Our findings reveal that Shh directly impacts its own distribution, thus providing a molecular explanation for the robustness of morphogenesis to both environmental insults and individual variability.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Among molecules that bridge environment, cell metabolism, and cell signaling, hydrogen peroxide (H2O2) recently appeared as an emerging but central player. Its level depends on cell metabolism and environment and was recently shown to play key roles during embryogenesis, contrasting with its long-established role in disease progression. We decided to explore whether the secreted morphogen Sonic hedgehog (Shh), known to be essential in a variety of biological processes ranging from embryonic development to adult tissue homeostasis and cancers, was part of these interactions. Here, we report that H2O2 levels control key steps of Shh delivery in cell culture: increased levels reduce primary secretion, stimulate endocytosis and accelerate delivery to recipient cells; in addition, physiological in vivo modulation of H2O2 levels changes Shh distribution and tissue patterning. Moreover, a feedback loop exists in which Shh trafficking controls H2O2 synthesis via a non-canonical BOC-Rac1 pathway, leading to cytoneme growth. Our findings reveal that Shh directly impacts its own distribution, thus providing a molecular explanation for the robustness of morphogenesis to both environmental insults and individual variability. |
NADPH-Oxidase Derived Hydrogen Peroxide and Irs2b Facilitate Re-oxygenation-Induced Catch-Up Growth in Zebrafish Embryo Article de journal Ayaka Zasu; Futa Hishima; Marion Thauvin; Yosuke Yoneyama; Yoichiro Kitani; Fumihiko Hakuno; Michel Volovitch; Shin-Ichiro Takahashi; Sophie Vriz; Christine Rampon; Hiroyasu Kamei Frontiers in Endocrinology, 13 , 2022, ISSN: 1664-2392. @article{zasu_nadph-oxidase_2022, title = {NADPH-Oxidase Derived Hydrogen Peroxide and Irs2b Facilitate Re-oxygenation-Induced Catch-Up Growth in Zebrafish Embryo}, author = {Ayaka Zasu and Futa Hishima and Marion Thauvin and Yosuke Yoneyama and Yoichiro Kitani and Fumihiko Hakuno and Michel Volovitch and Shin-Ichiro Takahashi and Sophie Vriz and Christine Rampon and Hiroyasu Kamei}, url = {https://www.frontiersin.org/articles/10.3389/fendo.2022.929668}, issn = {1664-2392}, year = {2022}, date = {2022-01-01}, urldate = {2023-10-31}, journal = {Frontiers in Endocrinology}, volume = {13}, abstract = {Oxygen deprivation induces multiple changes at the cellular and organismal levels, and its re-supply also brings another special physiological status. We have investigated the effects of hypoxia/re-oxygenation on embryonic growth using the zebrafish model: hypoxia slows embryonic growth, but re-oxygenation induces growth spurt or catch-up growth. The mitogen-activated kinase (MAPK)-pathway downstream insulin-like growth factor (IGF/Igf) has been revealed to positively regulate the re-oxygenation-induced catch-up growth, and the role of reactive oxygen species generated by environmental oxygen fluctuation is potentially involved in the phenomenon. Here, we report the role of NADPH-oxidase (Nox)-dependent hydrogen peroxide (H2O2) production in the MAPK-activation and catch-up growth. The inhibition of Nox significantly blunted catch-up growth and MAPK-activity. Amongst two zebrafish insulin receptor substrate 2 genes (irs2a and irs2b), the loss of irs2b, but not its paralog irs2a, resulted in blunted MAPK-activation and catch-up growth. Furthermore, irs2b forcedly expressed in mammalian cells allowed IGF-MAPK augmentation in the presence of H2O2, and the irs2b deficiency completely abolished the somatotropic action of Nox in re-oxygenation condition. These results indicate that redox signaling alters IGF/Igf signaling to facilitate hypoxia/re-oxygenation-induced embryonic growth compensation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxygen deprivation induces multiple changes at the cellular and organismal levels, and its re-supply also brings another special physiological status. We have investigated the effects of hypoxia/re-oxygenation on embryonic growth using the zebrafish model: hypoxia slows embryonic growth, but re-oxygenation induces growth spurt or catch-up growth. The mitogen-activated kinase (MAPK)-pathway downstream insulin-like growth factor (IGF/Igf) has been revealed to positively regulate the re-oxygenation-induced catch-up growth, and the role of reactive oxygen species generated by environmental oxygen fluctuation is potentially involved in the phenomenon. Here, we report the role of NADPH-oxidase (Nox)-dependent hydrogen peroxide (H2O2) production in the MAPK-activation and catch-up growth. The inhibition of Nox significantly blunted catch-up growth and MAPK-activity. Amongst two zebrafish insulin receptor substrate 2 genes (irs2a and irs2b), the loss of irs2b, but not its paralog irs2a, resulted in blunted MAPK-activation and catch-up growth. Furthermore, irs2b forcedly expressed in mammalian cells allowed IGF-MAPK augmentation in the presence of H2O2, and the irs2b deficiency completely abolished the somatotropic action of Nox in re-oxygenation condition. These results indicate that redox signaling alters IGF/Igf signaling to facilitate hypoxia/re-oxygenation-induced embryonic growth compensation. |
2021 |
Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil–Gold Nanoparticle Complexes Article de journal Vladimir Mulens-Arias; Alba Nicolás-Boluda; Amandine Pinto; Alice Balfourier; Florent Carn; Amanda K A Silva; Marc Pocard; Florence Gazeau ACS Nano, 15 (2), p. 3330–3348, 2021, ISSN: 1936-0851, 1936-086X. @article{mulens-arias_tumor-selective_2021, title = {Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil\textendashGold Nanoparticle Complexes}, author = {Vladimir Mulens-Arias and Alba Nicol\'{a}s-Boluda and Amandine Pinto and Alice Balfourier and Florent Carn and Amanda K A Silva and Marc Pocard and Florence Gazeau}, url = {https://pubs.acs.org/doi/10.1021/acsnano.0c10276}, doi = {10.1021/acsnano.0c10276}, issn = {1936-0851, 1936-086X}, year = {2021}, date = {2021-02-01}, urldate = {2022-04-29}, journal = {ACS Nano}, volume = {15}, number = {2}, pages = {3330--3348}, abstract = {Peritoneal metastasis (PM) is considered as the terminal stage of metastatic colon cancer, with still poor median survival rate even with the best recent chemotherapy treatment. The current PM treatment combines cytoreductive surgery, which consists of resecting all macroscopic tumors, with hyperthermic intraperitoneal chemotherapy (HIPEC), which uses mild hyperthermia to boost the diffusion and cytotoxic effect of chemotherapeutic drugs. As HIPEC is performed via a closed circulation of a hot liquid containing chemotherapy, it induces uncontrolled heating and drug distribution in the whole peritoneal cavity with important off-site toxicity and a high level of morbidity. Here, we propose a safer precision strategy using near-infrared (NIR) photoactivated gold nanoparticles (AuNPs) coupled to the chemotherapeutic drug 5-fluorouracil (5-FU) to enable a spatial and temporal control of mild chemo-hyperthermia targeted to the tumor nodules within the peritoneal cavity. Both the 16 nm AuNPs and the corresponding complex with 5-FU (AuNP−5-FU) were shown as efficient NIR photothermal agents in the microenvironment of subcutaneous colon tumors as well as PM in syngeneic mice. Noteworthy, NIR photothermia provided additional antitumor effects to 5-FU treatment. A single intraperitoneal administration of AuNP−5-FU resulted in their preferential accumulation in tumor nodules and peritoneal macrophages, allowing light-induced selective hyperthermia, extended tumor necrosis, and activation of a pro-inflammatory immune response while leaving healthy tissues without any damage. From a translational standpoint, the combined and tumor-targeted photothermal and chemotherapy mediated by the AuNP−drug complex has the potential to overcome the current off-target toxicity of HIPEC in clinical practice.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Peritoneal metastasis (PM) is considered as the terminal stage of metastatic colon cancer, with still poor median survival rate even with the best recent chemotherapy treatment. The current PM treatment combines cytoreductive surgery, which consists of resecting all macroscopic tumors, with hyperthermic intraperitoneal chemotherapy (HIPEC), which uses mild hyperthermia to boost the diffusion and cytotoxic effect of chemotherapeutic drugs. As HIPEC is performed via a closed circulation of a hot liquid containing chemotherapy, it induces uncontrolled heating and drug distribution in the whole peritoneal cavity with important off-site toxicity and a high level of morbidity. Here, we propose a safer precision strategy using near-infrared (NIR) photoactivated gold nanoparticles (AuNPs) coupled to the chemotherapeutic drug 5-fluorouracil (5-FU) to enable a spatial and temporal control of mild chemo-hyperthermia targeted to the tumor nodules within the peritoneal cavity. Both the 16 nm AuNPs and the corresponding complex with 5-FU (AuNP−5-FU) were shown as efficient NIR photothermal agents in the microenvironment of subcutaneous colon tumors as well as PM in syngeneic mice. Noteworthy, NIR photothermia provided additional antitumor effects to 5-FU treatment. A single intraperitoneal administration of AuNP−5-FU resulted in their preferential accumulation in tumor nodules and peritoneal macrophages, allowing light-induced selective hyperthermia, extended tumor necrosis, and activation of a pro-inflammatory immune response while leaving healthy tissues without any damage. From a translational standpoint, the combined and tumor-targeted photothermal and chemotherapy mediated by the AuNP−drug complex has the potential to overcome the current off-target toxicity of HIPEC in clinical practice. |
Arnaud Gautier; Ludovic Jullien; Chenge Li; Marie-Aude Plamont; Alison G Tebo; Marion Thauvin; Michel Volovitch; Sophie Vriz Springer US, New York, NY, 2021, ISBN: 978-1-07-161593-5. @book{gautier_versatile_2021, title = {Versatile On-Demand Fluorescent Labeling of Fusion Proteins Using Fluorescence-Activating and Absorption-Shifting Tag (FAST)}, author = {Arnaud Gautier and Ludovic Jullien and Chenge Li and Marie-Aude Plamont and Alison G Tebo and Marion Thauvin and Michel Volovitch and Sophie Vriz}, editor = {Eli Zamir}, url = {https://doi.org/10.1007/978-1-0716-1593-5_16}, doi = {10.1007/978-1-0716-1593-5_16}, isbn = {978-1-07-161593-5}, year = {2021}, date = {2021-01-01}, urldate = {2023-10-31}, booktitle = {Multiplexed Imaging: Methods and Protocols}, pages = {253--265}, publisher = {Springer US}, address = {New York, NY}, series = {Methods in Molecular Biology}, abstract = {Observing the localization, the concentration, and the distribution of proteins in cells or organisms is essential to understand theirs functions. General and versatile methods allowing multiplexed imaging of proteins under a large variety of experimental conditions are thus essential for deciphering the inner workings of cells and organisms. Here, we present a general method based on the non-covalent labeling of a small protein tag, named FAST (fluorescence-activating and absorption-shifting tag), with various fluorogenic ligands that light up upon labeling, which makes the simple, robust, and versatile on-demand labeling of fusion proteins in a wide range of experimental systems possible.}, keywords = {}, pubstate = {published}, tppubtype = {book} } Observing the localization, the concentration, and the distribution of proteins in cells or organisms is essential to understand theirs functions. General and versatile methods allowing multiplexed imaging of proteins under a large variety of experimental conditions are thus essential for deciphering the inner workings of cells and organisms. Here, we present a general method based on the non-covalent labeling of a small protein tag, named FAST (fluorescence-activating and absorption-shifting tag), with various fluorogenic ligands that light up upon labeling, which makes the simple, robust, and versatile on-demand labeling of fusion proteins in a wide range of experimental systems possible. |
Rhenium carbonyl complexes bearing methylated triphenylphosphonium cations as antibody-free mitochondria trackers for X-ray fluorescence imaging Article de journal Gabrielle Schanne; Lucas Henry; How Chee Ong; Andrea Somogyi; Kadda Medjoubi; Nicolas Delsuc; Clotilde Policar; Felipe García; Helene C Bertrand Inorg. Chem. Front., 8 , p. 3905-3915, 2021. @article{D1QI00542A, title = {Rhenium carbonyl complexes bearing methylated triphenylphosphonium cations as antibody-free mitochondria trackers for X-ray fluorescence imaging}, author = {Gabrielle Schanne and Lucas Henry and How Chee Ong and Andrea Somogyi and Kadda Medjoubi and Nicolas Delsuc and Clotilde Policar and Felipe Garc\'{i}a and Helene C Bertrand}, url = {http://dx.doi.org/10.1039/D1QI00542A}, doi = {10.1039/D1QI00542A}, year = {2021}, date = {2021-01-01}, journal = {Inorg. Chem. Front.}, volume = {8}, pages = {3905-3915}, publisher = {The Royal Society of Chemistry}, abstract = {Synchrotron Radiation X-ray Fluorescence (SXRF) imaging is a powerful technique for the visualization of metal complexes in biological systems. However, due to the lack of an endogenous elemental signature for mitochondria, probes for the localization of this organelle are required for colocalization studies. In this work, we designed and synthesized rhenium pyta tricarbonyl complexes conjugated to methylated triphenylphosphonium TP*P+ cations as multimodal probes for the visualization of mitochondria, suitable for fluorescence and SXRF imaging and quantification. Accumulation of the methylated triphenylphosphonium TP*P+-based conjugates in cells was observed in fixed A549 cells, and the amount of mitochondrial uptake was linked to the lipophilicity of the TPP+ vector. Our work highlights a convenient rhenium-based multimodal mitochondrial-targeted probe compatible with SXRF nano-imaging.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Synchrotron Radiation X-ray Fluorescence (SXRF) imaging is a powerful technique for the visualization of metal complexes in biological systems. However, due to the lack of an endogenous elemental signature for mitochondria, probes for the localization of this organelle are required for colocalization studies. In this work, we designed and synthesized rhenium pyta tricarbonyl complexes conjugated to methylated triphenylphosphonium TP*P+ cations as multimodal probes for the visualization of mitochondria, suitable for fluorescence and SXRF imaging and quantification. Accumulation of the methylated triphenylphosphonium TP*P+-based conjugates in cells was observed in fixed A549 cells, and the amount of mitochondrial uptake was linked to the lipophilicity of the TPP+ vector. Our work highlights a convenient rhenium-based multimodal mitochondrial-targeted probe compatible with SXRF nano-imaging. |
A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme Article de journal Koudedja Coulibaly; Marion Thauvin; Adyn Melenbacher; Clara Testard; Evangelina Trigoni; Amandine Vincent; Martin J Stillman; Sophie Vriz; Clotilde Policar; Nicolas Delsuc Inorganic Chemistry, 60 (13), p. 9309-9319, 2021. @article{doi:10.1021/acs.inorgchem.0c03718b, title = {A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme}, author = {Koudedja Coulibaly and Marion Thauvin and Adyn Melenbacher and Clara Testard and Evangelina Trigoni and Amandine Vincent and Martin J Stillman and Sophie Vriz and Clotilde Policar and Nicolas Delsuc}, url = {https://doi.org/10.1021/acs.inorgchem.0c03718}, doi = {10.1021/acs.inorgchem.0c03718}, year = {2021}, date = {2021-01-01}, journal = {Inorganic Chemistry}, volume = {60}, number = {13}, pages = {9309-9319}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models Article de journal Amandine Vincent; Marion Thauvin; Elodie Quévrain; Emilie Mathieu; Sarah Layani; Philippe Seksik; Ines Batinic-Haberle; Sophie Vriz; Clotilde Policar; Nicolas Delsuc Journal of Inorganic Biochemistry, p. 111431, 2021, ISSN: 0162-0134. @article{VINCENT2021111431, title = {Evaluation of the compounds commonly known as superoxide dismutase and catalase mimics in cellular models}, author = {Amandine Vincent and Marion Thauvin and Elodie Qu\'{e}vrain and Emilie Mathieu and Sarah Layani and Philippe Seksik and Ines Batinic-Haberle and Sophie Vriz and Clotilde Policar and Nicolas Delsuc}, url = {https://www.sciencedirect.com/science/article/pii/S0162013421000787}, doi = {https://doi.org/10.1016/j.jinorgbio.2021.111431}, issn = {0162-0134}, year = {2021}, date = {2021-01-01}, journal = {Journal of Inorganic Biochemistry}, pages = {111431}, abstract = {Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2′-nbutoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5, 6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1, 4, 7, 10] tetra--azacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N′-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress that results from an imbalance between the concentrations of reactive species (RS) and antioxidant defenses is associated with many pathologies. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase are among the key enzymes that maintain the low nanomolar physiological concentrations of superoxide and hydrogen peroxide. The increase in the levels of these species and their progeny could have deleterious effects. In this context, chemists have developed SOD and CAT mimics to supplement them when cells are overwhelmed with oxidative stress. However, the beneficial activity of such molecules in cells depends not only on their intrinsic catalytic activities but also on their stability in biological context, their cell penetration and their cellular localization. We have employed cellular assays to characterize several compounds that possess SOD and CAT activities and have been frequently used in cellular and animal models. We used cellular assays that address SOD and CAT activities of the compounds. Finally, we determined the effect of compounds on the suppression of the inflammation in HT29-MD2 cells challenged by lipopolysaccharide. When the assay requires penetration inside cells, the SOD mimics Mn(III) meso-tetrakis(N-(2′-nbutoxyethyl)pyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP5+) and Mn(II) dichloro[(4aR,13aR,17aR,21aR)-1,2,3,4,4a,5, 6,12,13,13a,14,15,16,17,17a,18,19,20,21,21a-eicosahydro-11,7-nitrilo-7Hdibenzo[b,h] [1, 4, 7, 10] tetra--azacycloheptadecine-κN5,κN13,κN18,κN21,κN22] (Imisopasem manganese, M40403, CG4419) were found efficacious at 10 μM, while Mn(II) chloro N-(phenolato)-N,N′-bis[2-(N-methyl-imidazolyl)methyl]-ethane-1,2-diamine (Mn1) requires an incubation at 100 μM. This study thus demonstrates that MnTnBuOE-2-PyP5+, M40403 and Mn1 were efficacious in suppressing inflammatory response in HT29-MD2 cells and such action appears to be related to their ability to enter the cells and modulate reactive oxygen species (ROS) levels. |
Orthogonal fluorescent chemogenetic reporters for multicolor imaging Article de journal Alison G Tebo; Benjamien Moeyaert; Marion Thauvin; Irene Carlon-Andres; Dorothea Böken; Michel Volovitch; Sergi Padilla-Parra; Peter Dedecker; Sophie Vriz; Arnaud Gautier Nature Chemical Biology, 17 (1), p. 30–38, 2021, ISSN: 1552-4469. @article{tebo_orthogonal_2021, title = {Orthogonal fluorescent chemogenetic reporters for multicolor imaging}, author = {Alison G Tebo and Benjamien Moeyaert and Marion Thauvin and Irene Carlon-Andres and Dorothea B\"{o}ken and Michel Volovitch and Sergi Padilla-Parra and Peter Dedecker and Sophie Vriz and Arnaud Gautier}, doi = {10.1038/s41589-020-0611-0}, issn = {1552-4469}, year = {2021}, date = {2021-01-01}, journal = {Nature Chemical Biology}, volume = {17}, number = {1}, pages = {30--38}, abstract = {Spectrally separated fluorophores allow the observation of multiple targets simultaneously inside living cells, leading to a deeper understanding of the molecular interplay that regulates cell function and fate. Chemogenetic systems combining a tag and a synthetic fluorophore provide certain advantages over fluorescent proteins since there is no requirement for chromophore maturation. Here, we present the engineering of a set of spectrally orthogonal fluorogen-activating tags based on the fluorescence-activating and absorption shifting tag (FAST) that are compatible with two-color, live-cell imaging. The resulting tags, greenFAST and redFAST, demonstrate orthogonality not only in their fluorogen recognition capabilities, but also in their one- and two-photon absorption profiles. This pair of orthogonal tags allowed the creation of a two-color cell cycle sensor capable of detecting very short, early cell cycles in zebrafish development and the development of split complementation systems capable of detecting multiple protein-protein interactions by live-cell fluorescence microscopy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Spectrally separated fluorophores allow the observation of multiple targets simultaneously inside living cells, leading to a deeper understanding of the molecular interplay that regulates cell function and fate. Chemogenetic systems combining a tag and a synthetic fluorophore provide certain advantages over fluorescent proteins since there is no requirement for chromophore maturation. Here, we present the engineering of a set of spectrally orthogonal fluorogen-activating tags based on the fluorescence-activating and absorption shifting tag (FAST) that are compatible with two-color, live-cell imaging. The resulting tags, greenFAST and redFAST, demonstrate orthogonality not only in their fluorogen recognition capabilities, but also in their one- and two-photon absorption profiles. This pair of orthogonal tags allowed the creation of a two-color cell cycle sensor capable of detecting very short, early cell cycles in zebrafish development and the development of split complementation systems capable of detecting multiple protein-protein interactions by live-cell fluorescence microscopy. |
2020 |
Extracellular Pax6 Regulates Tangential Cajal–Retzius Cell Migration in the Developing Mouse Neocortex Article de journal H Kaddour; E Coppola; A A Di Nardo; C Le Poupon; P Mailly; A Wizenmann; M Volovitch; A Prochiantz; A Pierani Cerebral Cortex, 30 (2), p. 465–475, 2020, ISSN: 1047-3211. @article{kaddour_extracellular_2020, title = {Extracellular Pax6 Regulates Tangential Cajal\textendashRetzius Cell Migration in the Developing Mouse Neocortex}, author = {H Kaddour and E Coppola and A A Di Nardo and C Le Poupon and P Mailly and A Wizenmann and M Volovitch and A Prochiantz and A Pierani}, url = {https://doi.org/10.1093/cercor/bhz098}, doi = {10.1093/cercor/bhz098}, issn = {1047-3211}, year = {2020}, date = {2020-01-01}, urldate = {2023-10-31}, journal = {Cerebral Cortex}, volume = {30}, number = {2}, pages = {465--475}, abstract = {The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal\textendashRetzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal–Retzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development. |
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. |
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. |