title: Myocardial Ischemic Postconditioning Promotes Autophagy against Ischemia Reperfusion Injury via the Activation of the nNOS/AMPK/mTOR Pathway.
abstract: Autophagy participates in the progression of many diseases, comprising ischemia/ reperfusion (I/R). It is reported that it is involved in the protective mechanism of ischemic postconditioning (IPostC). According to research, neuronal nitric oxide synthase (nNOS) is also involved in the condition of I/R and IPostC. However, the relationship between nNOS, autophagy and IPostC has not been previously investigated. We hypothesize that IPostC promotes autophagy activity against I/R injury partially through nNOS-mediated pathways. Mouse hearts were subjected to I/R injury through the ligation of the left anterior descending coronary artery. H9c2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro. IPostC, compared with I/R, restored nNOS activity, increased the formation of autophagosome and restored the impaired autophagic flux, thus autophagic activity was raised markedly. IPostC increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and suppressed mammalian target of rapamycin (mTOR), but a selective nNOS inhibitor abolished those effects. Similar effects of IPostC were demonstrated in H9c2 cells in vitro. IPostC decreased infarct size and preserved most of the normal structure. The level of reactive oxygen species (ROS) and cell apoptosis were reduced by IPostC with improved cell viability and mitochondrial membrane potential. However, an autophagy inhibitor suppressed the protective effects. These results suggest that IPostC promoted autophagy against I/R injury at least partially via the activation of nNOS/AMPK/mTOR pathway.
authors.affiliation: Department of Pharmacology, Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 211166, China. maojhao@163.com.
authors.forename: Maojuan
authors.initials: M
authors.lastname: Hao
authors.affiliation: Department of Pharmacology, Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 211166, China. zshnjmu@163.com.
authors.forename: Suhua
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 211166, China. lianghu@njmu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 211166, China. zhuhongyi0217@sina.cn.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 211166, China. 15240242832@sina.cn.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Nanjing Medical University, Nanjing 211166, China. pharm_qpli@njmu.edu.cn.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D057775:Ischemic Postconditioning; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D052248:Nitric Oxide Synthase Type I; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: adenosine monophosphate-activated protein kinase (AMPK); autophagy; ischemia/reperfusion; ischemic postconditioning (IPostC); mammalian target of rapamycin (mTOR); neuronal nitric oxide synthase (nNOS)