Non-enzymatic oxidized metabolites of polyunsaturated fatty acids Omega-3 and normal and pathological muscle function
The cardioprotective role of omega-3 polyunsaturated fatty acids (PUFA ω3) has been known since the 1970s. Progressively, many laboratories have attempted to understand the origin of this cardioprotection which mainly following a myocardial infarction but none consensus made is yet found. In collaboration with chemists IBMM, we hypothesized that these are not the fatty acids themselves are active but the oxidation products of these lipids.
Indeed, following myocardial many reactive oxygen species are produced and oxidize proteins, nucleic acids and cellular lipids. If the membrane is enriched in ω3 PUFAs such as DHA (C22: 6n-3), there will be among the products of non-enzymatic metabolites neuroprostanes. We seek to identify and understand how these neuroprostanes modulate cardiac cell physiology.
- Thierry Durand, Camille Oger, Jean-Marie Galano (IBMM Montpellier),
- Stéfan Matecki, Alain. Lacampagne (équipe 2 du laboratoire).
Major Publications :
- Galano J-M., Mas E., Barden A., Mori T., Signorini C., De Felice C., Barrett A., Opere C., Pinot E., Schwedhelm E., Benndorf R., Roy J., Le Guennec J-Y., Oger C., Durand T Isoprostanes and neuroprostanes: total synthesis, biological activity and biomarkers of oxidative stress in humans. Prostaglandins and Other Lipid Mediators. 2013, 107 : 95-102.
- Galano J-M., Lee J., Gladine C., Conte B., Le Guennec J-Y., Oger C. & Durand T. Non-enzymatic cyclic oxygenated metabolites of adrenic, docosahexaenoic, eicosapentaenoic and α-linolenic acids; bioactivities and potential use as biomarkers.BBA 2015 1851(4):446-455.
- Roy J, Oger C, Thireau J, Roussel J, Mercier-Touzet O, Faure D, Pinot E, Farah C, Taber DF, Cristol JP, JCY, Lacampagne A, Galano JM, Durand T, Le Guennec JY. . “Non-enzymatic lipid mediators, neuroprostanes, exert the anti-arrhythmic properties of docosahexaenoic acid. “ . Free Radical Biology and Medicine. 2015, 86: 269-278.
- Roy J, Le Guennec JY, Galano JM, Thireau J, Bultel-Poncé V, Demion M, Oger C, Lee JC, Durand T. (2015). “Non-enzymatic cyclic oxygenated metabolites of omega-3 polyunsaturated fatty acid: Bioactive drugs? “ Biochimie, in press.
- V. Bultel-Poncé, T. Durand, J-M Galano, J-Y Le Guennec, C. Oger, Roy, J. Thireau. « Methods and pharmaceutical composition for the treatment and prevention of cardiac arrhythmias ». Numéro d’application : WO2014086819.
- A. Lacampagne, A. Guy, C. Oger, H. Dridi, J-M Galano, J-Y Le Guennec, J. Roy, S. Matecki, T. Durand, Thireau, V. Bultel. « Methods and pharmaceutical compositions for the treatment of disorders or diseases associated with ryanodine receptor dysfunction ». Numéro d’application : EP14305977.2 du 23/06/2014.