A Cell-Penetrant Manganese SOD-Mimic Is Able To Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases

Emilie Mathieu (1, 2, 3, 4, 5, 6) , Anne-Sophie Bernard (3, 1, 4, 5, 6) , Nicolas Delsuc (1, 2, 3, 5, 6, 4) , Elodie Quévrain (7, 1, 3, 4) , Géraldine Gazzah (1, 2, 3, 4) , Barry Lai (8) , Florian Chain (9) , Philippe Langella (9) , Maria Bachelet (1, 7, 9) , Joelle Masliah (1, 7, 4) , Philippe Seksik (1, 7, 4) , Clotilde Policar (1, 2, 3, 4, 5, 6)

1 Département de Chimie - ENS-PSL
2 LBM-E1 - Peptides, glycoconjugués et métaux en biologie
3 UPMC - Université Pierre et Marie Curie - Paris 6
4 LBM UMR 7203 - Laboratoire des biomolécules
5 INC-CNRS - Institut de Chimie - CNRS Chimie
6 PSL - Université Paris Sciences et Lettres
7 LBM-E4 - Microorganismes, Molécules Bioactives et Physiopathologie Intestinale
8 XSD - X-ray Science Division
9 Commensal and probiotics-host interactions laboratory

Inorganic complexes are increasingly used for biological and medicinal applications and the question of the cell-penetration and of the cell-distribution of metal-lodrugs is key to understand their biological activity. Oxi-dative 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 a Mn-complex Mn1 mimicking superoxide dismutase, a protein involved in the cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining investigation of Mn1 intracellular speciation using mass spectrometry, 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 find the MS-signature of Mn1 in cell lysates and quantified the overall Mn-content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. Mn1 exerts an intra-cellular anti-inflammatory activity, remains at least partially coordinated, with a diffuse distribution over the whole cell and functionally complements mitochondrial MnSOD.

Mots clés: Supporting Information Placeholder; SOD mimics — anti-inflammatory agent — manganese complex — imaging — metal speciation —inorganic cel-; lular chemistry

Domaines: Chimie

Emilie Mathieu, Anne-Sophie Bernard, Nicolas Delsuc, Elodie Quévrain, Géraldine Gazzah, et al.. A Cell-Penetrant Manganese SOD-Mimic Is Able To Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases. Inorganic Chemistry, 2017, 56 (5), pp.2545-2555. ⟨10.1021/acs.inorgchem.6b02695⟩. ⟨hal-01473825⟩