Non-enzymatic oxidized metabolite of DHA, 4(RS)-4-F_4t-neuroprostane protects the heart against reperfusion injury

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• 作者：J&eacute ; rô ; me Roy^a ; ^{jerome.roy1902@gmail.com} ; J&eacute ; r&eacute ; my Fauconnier^a ; Camille Oger^b ; Charlotte Farah^a ; Claire Angebault-Prouteau^c ; J&eacute ; rô ; me Thireau^a ; Patrice Bideaux^a ; Val&eacute ; rie Scheuermann^a ; Val&eacute ; rie Bultel-Ponc&eacute ; ^b ; Marie Demion^a ; Jean-Marie Galano^b ; Thierry Durand^b ; Jetty Chung-Yung Lee^d ; ¹ ; Jean-Yves Le Guennec^a ; ¹
• 关键词：ΔΨm ; mitochondrial membrane potential ; 4-F4t-NeuroP ; 4(RS)-4-F4t-neuroprostane ; n-3 PUFA ; n-3 polyunsaturated fatty acids ; Ca2+ ; Calcium ; CsA ; cyclosporine A ; CypD ; cyclosphilin D ; DHA ; docosahexaenoic acid ; ECG ; electrocardiogram ; EPA ; eicosapentaenoic acid ; VES ; ventricular extrasystoles ; FCCP ; carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone ; I/R ; ischemia-reperfusion ; mPTP ; mitochondrial permeability transition pore ; TMRM ; tetramethylrhodamine methyl ester ; ROS ; reactive oxygen species
• 刊名：Free Radical Biology and Medicine
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：102
• 期：Complete
• 页码：229-239
• 全文大小：1030 K
• 卷排序：102

文摘

The lipid mediator 4(RS)-4-F4t-neuroprostane derived from non-enzymatic peroxidation of DHA contributes to cardioprotective properties of this PUFA following an ischemia/reperfusion event. 4(RS)-4-F4t­neuroprostane displays a strong anti-apoptotic property involving the normalization of calcium homeostasis by the stabilization of ryanodine receptor complex and to a decrease of mPTP opening leading to the reduction of pro-apoptotic factors. This study suggests that some well-known effects of n-3 fatty acids are mediated by their non-enzymatic cyclic oxygenated metabolites. This discovery opens new perspectives for non-enzymatic oxidized products of n-3 polyunsaturated fatty acids as potent preventive therapeutic way in acute myocardial infarction.