Globular adiponectin protects rat hepatocytes against acetaminophen-induced cell death via modulation of the inflammasome activation and ER stress: Critical role of autophagy induction.

Globular adiponectin protects rat hepatocytes against acetaminophen-induced cell death via modulation of the inflammasome activation and ER stress: Critical role of autophagy induction. Biochem Pharmacol. 2018 May 24;154:278-292 Authors: Kim EH, Park PH Abstract Acetaminophen (APAP) overdose treatment causes severe liver injury. Adiponectin, a hormone predominantly produced by adipose tissue, exhibits protective effects against APAP-induced hepatotoxicity. However, the underlying mechanisms are not clearly understood. In the present study, we examined the protective effect of globular adiponectin (gAcrp) on APAP-induced hepatocyte death and its underlying mechanisms. We found that APAP (2 mM)-induced hepatocyte death was prevented by inhibition of the inflammasome. In addition, treatment with gAcrp (0.5 and 1 μg/ml) inhibited APAP-induced activation of the inflammasome, judged by suppression of interleukin-1β maturation, caspase-1 activation, and apoptosis-associated speck-like protein (ASC) speck formation, suggesting that protective effects of gAcrp against APAP-induced hepatocyte death is mediated via modulation of the inflammasome. APAP also induced ER stress and treatment with tauroursodeoxycholic acid (TUDCA), an ER chaperone and inhibitor of ER stress, abolished APAP-induced inflammasomes activation, implying that ER stress acts as signaling event leading to the inflammasome activation in hepatocytes stimulated with APAP...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research