Modulation of Atg5 Expression by Globular Adiponectin Contributes to Autophagy Flux and Suppression of Ethanol-Induced Cell Death in Liver Cells.

Modulation of Atg5 Expression by Globular Adiponectin Contributes to Autophagy Flux and Suppression of Ethanol-Induced Cell Death in Liver Cells. Food Chem Toxicol. 2014 Feb 26; Authors: Nepal S, Kim MJ, Lee ES, Kim JA, Choi DY, Sohn DH, Lee SH, Song K, Kim SH, Jeong GS, Jeong TC, Park PH Abstract Globular adiponectin (gAcrp) protects liver cells from ethanol-induced apoptosis via induction of autophagy. However, the underlying mechanisms are unknown. The present study aims to investigate the potential role of autophagy-related protein 5 (Atg5), an essential Atg for the elongation of autophagosomes, in suppression of ethanol-induced cytotoxicity by gAcrp. Here, we demonstrated that suppression of Atg5 expression by ethanol was restored by pretreatment with gAcrp both in primary rat hepatocytes and human hepatoma cell line (HepG2). Moreover, ethanol-induced accumulation of p62 (sequestosome1), a marker of autophagic flux, was restored by gAcrp treatment, implying that gAcrp modulates autophagic flux in liver cells. Further, Atg5 silencing prevented p62 degradation by gAcrp, suggesting that Atg5 plays a critical role in induction of autophagic flux by gAcrp. Interestingly, gene silencing of Atg5 by siRNA abrogated restoration of autophagosome formation by gAcrp in ethanol-treated cells. Finally, protection of liver cells by gAcrp from ethanol-induced apoptosis was also significantly attenuated by knocking-down of Atg5 expression, suggesting an i...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research