title: A Cell-Penetrant Manganese Superoxide Dismutase (MnSOD) Mimic Is Able To Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases.
abstract: Inorganic complexes are increasingly used for biological and medicinal applications, and the question of the cell penetration and distribution of metallodrugs is key to understanding their biological activity. Oxidative stress is known to be involved in inflammation and in inflammatory bowel diseases for which antioxidative defenses are weakened. We report here the study of the manganese complex Mn1 mimicking superoxide dismutase (SOD), a protein involved in cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and found the MS signature of Mn1 in cell lysates and quantified the overall manganese content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. DNBS-induced colitis in mice was used to investigate Mn1 activity in vivo. Mn1 exerts an intracellular antiinflammatory activity, remains at least partially coordinated, with diffuse distribution over the whole cell, and functionally complements mitochondrial MnSOD.
authors.affiliation: Département de Chimie, Ecole Normale Superieure, PSL Research University, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolecules (LBM), 24 rue Lhomond, 75005 Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mathieu
authors.affiliation: Département de Chimie, Ecole Normale Superieure, PSL Research University, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolecules (LBM), 24 rue Lhomond, 75005 Paris, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Bernard
authors.affiliation: Département de Chimie, Ecole Normale Superieure, PSL Research University, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolecules (LBM), 24 rue Lhomond, 75005 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delsuc
authors.affiliation: Département de Chimie, Ecole Normale Superieure, PSL Research University, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolecules (LBM), 24 rue Lhomond, 75005 Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Quévrain
authors.affiliation: Département de Chimie, Ecole Normale Superieure, PSL Research University, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolecules (LBM), 24 rue Lhomond, 75005 Paris, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Gazzah
authors.affiliation: X-ray Science Division, Argonne National Laboratory (ANL) , Argonne, Illinois 60439, United States.
authors.forename: Barry
authors.initials: B
authors.lastname: Lai
authors.affiliation: Commensal and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, F-78350 Jouy-en-Josas, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Chain
authors.affiliation: Commensal and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, F-78350 Jouy-en-Josas, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.affiliation: Sorbonne Universites, UPMC Univ Paris 06 - Département de Chimie, Ecole Normale Superieure, PSL Research University - CNRS, INSERM, APHP, INRA, Laboratoire des Biomolecules (LBM), 27 rue de Chaligny, 75012 Paris, France.|Commensal and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, F-78350 Jouy-en-Josas, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Bachelet
authors.affiliation: Département de Chimie, Ecole Normale Superieure, PSL Research University, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolecules (LBM), 24 rue Lhomond, 75005 Paris, France.|Sorbonne Universites, UPMC Univ Paris 06 - Département de Chimie, Ecole Normale Superieure, PSL Research University - CNRS, INSERM, APHP, INRA, Laboratoire des Biomolecules (LBM), 27 rue de Chaligny, 75012 Paris, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Masliah
authors.affiliation: Sorbonne Universites, UPMC Univ Paris 06 - Département de Chimie, Ecole Normale Superieure, PSL Research University - CNRS, INSERM, APHP, INRA, Laboratoire des Biomolecules (LBM), 27 rue de Chaligny, 75012 Paris, France.|Commensal and Probiotics-Host Interactions Laboratory, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, F-78350 Jouy-en-Josas, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Seksik
authors.affiliation: Département de Chimie, Ecole Normale Superieure, PSL Research University, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolecules (LBM), 24 rue Lhomond, 75005 Paris, France.
authors.forename: Clotilde
authors.identifier: http://orcid.org/0000-0003-0255-1650
authors.initials: C
authors.lastname: Policar
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018925:Chemokines; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; C045305:2,4-dinitrofluorobenzene sulfonic acid; D004139:Dinitrofluorobenzene; D013482:Superoxide Dismutase