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JAK 2/ STAT 3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury
Author(s) -
Yang Yang,
Duan Weixun,
Jin Zhenxiao,
Yi Wei,
Yan Juanjuan,
Zhang Song,
Wang Ning,
Liang Zhenxing,
Li Yue,
Chen Wensheng,
Yi Dinghua,
Yu Shiqiang
Publication year - 2013
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12070
Subject(s) - melatonin , oxidative stress , superoxide dismutase , malondialdehyde , cardioprotection , reperfusion injury , oxidative phosphorylation , apoptosis , mitochondrion , chemistry , reactive oxygen species , stat3 , pharmacology , ischemia , biology , endocrinology , medicine , biochemistry
Ischemia/reperfusion injury ( IRI ) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Numerous data indicate that the JAK 2/ STAT 3 signaling pathway is specifically involved in preventing myocardial IRI . Melatonin has potent activity against IRI and may regulate JAK 2/ STAT 3 signaling. This study investigated the protective effect of melatonin pretreatment on myocardial IRI and elucidated its potential mechanism. Perfused isolated rat hearts and cultured neonatal rat cardiomyocytes were exposed to melatonin in the absence or presence of the JAK 2/ STAT 3 inhibitor AG 490 or JAK 2 si RNA and then subjected to IR . Melatonin conferred a cardio‐protective effect, as shown by improved postischemic cardiac function, decreased infarct size, reduced apoptotic index, diminished lactate dehydrogenase release, up‐regulation of the anti‐apoptotic protein Bcl2, and down‐regulation of the pro‐apoptotic protein Bax. AG 490 or JAK 2 si RNA blocked melatonin‐mediated cardio‐protection by inhibiting JAK 2/ STAT 3 signaling. Melatonin exposure also resulted in a well‐preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase ( SOD ) activity, and decreased formation of mitochondrial hydrogen peroxide (H 2 O 2 ) and malondialdehyde ( MDA ), which indicates that the IR ‐induced mitochondrial oxidative damage was significantly attenuated. However, this melatonin‐induced effect on mitochondrial function was reversed by AG 490 or JAK 2 si RNA treatment. In summary, our results demonstrate that melatonin pretreatment can attenuate IRI by reducing IR ‐induced mitochondrial oxidative damage via the activation of the JAK 2/ STAT 3 signaling pathway.