Ischemic postconditioning regulates cardiomyocyte autophagic activity following ischemia/reperfusion injury

Guo,Liang; Xu,Jun‑Mei; Mo,Xiao‑Ye

doi:10.3892/mmr.2015.3533

Ischemic postconditioning regulates cardiomyocyte autophagic activity following ischemia/reperfusion injury

Authors:
- Liang Guo
- Jun‑Mei Xu
- Xiao‑Ye Mo
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Affiliations: Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: March 24, 2015 https://doi.org/10.3892/mmr.2015.3533
Pages: 1169-1176

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Abstract

Ischemic postconditioning (IPostC) is a promising protective mechanism for combating reperfusion injury. However, the role of autophagy in the protective effects of IPostC and the associated signaling pathways have remained to be elucidated. Male Sprague Dawley rats were subjected to 30 min ischemia and 1, 2, 3, 6, 12 and 24 h of reperfusion, with or without IPostC treatment. Autophagic flux was evaluated by detecting mRNA and protein expression levels of microtubule associated protein 1 light chain 3 and p62. Phosphorylated (p)‑P70S6 kinase (P70S6K), p‑adenosine monophosphate‑activated kinase (AMPK) and Beclin 1 protein levels were measured by western blot analysis. Myocardial infarct size was measured using staining with Evans blue dye and myocardial apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining. Autophagic activity was observed to be inhibited within the first hour of reperfusion, increased during 2‑6 h and reduced from 12‑24 h following IPostC compared with reperfusion without IPostC. Inhibition of autophagy by chloroquine significantly reversed the effects of IPostC on myocardial infarct size and the levels of apoptosis. IPostC significantly increased Beclin 1 levels, inhibited AMPK activation and increased P70S6K activation within the first hour compared with reperfusion without IPostC. IPostC attenuated the upregulation of Beclin 1 levels, increased AMPK activation and reduced P70S6K activation between 2 and 12 h, and subsequently exerted the opposite effects on these molecules between 12 and 24 h. IPostC was demonstrated to regulate autophagic activity in a time‑dependent manner. The Beclin 1 and AMPK‑mammalian target of rapamycin signaling pathways are suggested to be involved in the regulation of IPostC in autophagy.

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