Augmenter of liver regeneration protects against ethanol-induced acute liver injury by promoting autophagy.

Augmenter of liver regeneration protects against ethanol-induced acute liver injury by promoting autophagy. Am J Pathol. 2018 Dec 13;: Authors: Liu L, Xie P, Li W, Wu Y, An W Abstract Alcoholic liver disease is associated with high morbidity and mortality, and treatment options are limited to date. Augmenter of liver regeneration (ALR) may protect against hepatic injury caused by chemical poisons, including ethanol. Autophagy appears to positively influence survival in cases of liver dysfunction, though the mechanisms are poorly understood. Here, we investigated the impact of ALR-induced autophagy in vitro and in vivo in an ethanol-induced model of acute liver injury. Decreased serum levels of alanine aminotransferase and aspartate aminotransferase and reduced histological lesions revealed that mice overexpressing ALR experienced less liver damage than wild-type mice. ALR-knockdown mice suffered more severe liver damage than wild-type. ALR-transfected HepG2 cells showed increased survival rates, improved maintenance of mitochondrial membrane potential, and increased ATP levels following EtOH treatment. The observed protection was associated with up-regulation of autophagy-markers including LC3-II, Beclin-1, and Atg5, and down-regulation of p62 by ALR. Autophagy was inhibited in ALR-knockdown mice and HepG2 cells, and the autophagy inhibitor bafilomycinA1 attenuated the protective effects of ALR. The results showed that p-mTOR was dow...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research