Authors: Dawei Wang, Yong Ma, Zhengtian Li, Kai Kang, Xueying Sun, Shangha Pan, Jizhou Wang, Huayang Pan, Lianxin Liu, Desen Liang and Hongchi Jiang

Dawei Wang

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China
These authors contributed equally to this work.

Yong Ma

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China
These authors contributed equally to this work.

Zhengtian Li

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China
These authors contributed equally to this work.

Kai Kang

Department of Intensive Care Unit; the First Affiliated Hospital of Harbin Medical University; Harbin, China

Xueying Sun

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China; Department of Molecular Medicine and Pathology; Faculty of Medical and Health Sciences; University of Auckland; Auckland, New Zealand

Shangha Pan

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China

Jizhou Wang

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China

Huayang Pan

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China

Lianxin Liu

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China

Desen Liang

Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China

Hongchi Jiang

Corresponding author: jianghc@yahoo.com.cn
Key Laboratory of Hepatosplenic Surgery; Department of General Surgery; the First Affiliated Hospital of Harbin Medical University; Harbin, China

Abstract:
Hydrogen sulphide (H₂S) exerts a protective effect in hepatic ischemia-reperfusion (I/R) injury. However, the exact mechanism of H₂S action remains largely unknown. This study was designed to investigate the role of the PtdIns3K-AKT1 pathways and autophagy in the protective effect of H₂S against hepatic I/R injury. Primary cultured mouse hepatocytes and livers with or without NaHS (a donor of H₂S) preconditioning were exposed to anoxia/reoxygenation (A/R) and I/R, respectively. In certain groups, they were also pretreated with LY294002 (AKT1-specific inhibitor), 3-methyladenine (3MA, autophagy inhibitor) or rapamycin (autophagy enhancer), alone or simultaneously. Cell viability, expression of P-AKT1, T-AKT1, LC3 and BECN1 were examined. The severity of liver injury was measured by the levels of serum aminotransferase and inflammatory cytokine, apoptosis and histological examination. GFP-LC3 redistribution and transmission electron microscopy were used to test the activity of autophagy. H₂S preconditioning activated PtdIns3K-AKT1 signaling in hepatocytes. LY294002 could abolish the AKT1 activation and attenuate the protective effect of H₂S on hepatocytes A/R and hepatic I/R injuries. H₂S suppressed hepatic autophagy in vitro and in vivo. Further reducing autophagy by 3MA also diminished the protective effect of H₂S, while rapamycin could reverse the autophagy inhibitory effect and enhance the protective effect of H₂S against hepatocytes A/R and hepatic I/R injuries, consequently. Taken together, H₂S protects against hepatocytic A/R and hepatic I/R injuries, at least in part, through AKT1 activation but not autophagy. An autophagy agonist could be applied to potentiate this hepatoprotective effect by reversing the autophagy inhibition of H₂S.

Received: November 6, 2011; Accepted: March 6, 2012; Published Online: June 1, 2012

Preview: