Hydrogen sulfide protects against myocardial ischemia and reperfusion injury by activating AMP-activated protein kinase to restore autophagic flux

Hong Xie, Qingrong Xu, Jia Jia, Guizhen Ao, Ying Sun, Lifang Hu, Nabil J. Alkayed, Chen Wang, Jian Cheng

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

How hydrogen sulfide (H2S) protects against myocardial ischemia-reperfusion (I/R) injury is poorly understood. By using a slow-releasing H2S donor, we investigated if H2S protected against myocardial I/R injury by activating AMPK and restoring I/R-impaired autophagic flux. Male rats received anterior descending coronary artery occlusion followed by reperfusion. The H2S donor ADT and/or the AMPK inhibitor, compound C (CC), were administered after occlusion. Infarction was analyzed histologically. AMPK activation was assessed in the ischemic heart by analyzing phosphorylation of AMPK and S6 ribosomal protein. Autophagy was assessed by analyzing the following markers: microtubule-associated protein 1 light chain 3 (LC3) I and II, lysosome associated membrane protein-2 (LAMP-2), P62 and beclin-1. We further investigated if blocking autophagic flux with chloroquine abolished ADT cardioprotection in vivo. Myocardial I/R reduced serum H2S levels, which was elevated by ADT. ADT enhanced AMPK activation and reduced infarction following I/R, and both effects were abolished by AMPK inhibition. Myocardial I/R induced autophagosome accumulation, as evidenced by the increased ratios of LC3-II/LC3-I, upregulation of beclin-1 and P62 and reduction in LAMP-2. ADT blunted these autophagic changes induced by I/R, indicating that ADT restored I/R-impaired autophagic flux. The AMPK inhibitor CC blocked ADT effects on restoring I/R-impaired autophagy flux. Moreover, chloroquine pretreatment abolished cardioprotection of ADT and increased autophagosome accumulation in the ADT-treated heart following I/R. In conclusion, AMPK activation and subsequent restoration of I/R-impaired autophagic flux are unrecognized mechanisms underlying cardioprotective effects conferred by H2S donors.

Original languageEnglish (US)
Pages (from-to)632-638
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume458
Issue number3
DOIs
StatePublished - Mar 13 2015

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Keywords

  • AMP-activated protein kinase
  • Autophagy
  • Hydrogen sulfide
  • Myocardial ischemia/reperfusion

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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