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      • Globular adiponectin inhibits ethanol-induced apoptosis in HepG2 cells through heme oxygenase-1 induction

        ( Saroj Nepal ),( Mi Jin Kim ),( Amit Subedi ),( Eung Seok Lee ),( Chul Soon Yong ),( Jung Ae Kim ),( Wonku Kang ),( Mi Kyung Kwak ),( Dharamvie Singh Arya ),( Pil Hoon Park ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

        Hepatocellular apoptosis is an essential pathological feature of alcoholic liver disease. Adiponectin, an adipokine predominantly secreted from adipose tissue, has been shown to play beneficial roles in alcoholic liver disease against various inflammatory and pro-apoptotic molecules. However, the effects of adiponectin on ethanol-induced apoptosis in liver cells are largely unknown. Herein, we investigated the role of globularadiponectin (gAcrp) in the prevention of ethanol-induced apoptosis and further tried to decipher the potential mechanisms involved. In the present study, we demonstrated that gAcrp significantly inhibits both ethanol-induced increase in Fas ligand expression and activation of caspase-3 in human hepatoma cell lines (HepG2 cells), suggesting that gAcrp plays a protective role against ethanol-induced apoptosis in liver cells. This protective effect of gAcrp was mediated through adiponectin receptor R1 (adipoR1). Further, globular adiponectin treatment caused induction of heme oxygenase-1 (HO-1) through, at least in part, nuclear factor (erythroid-derived 2)-like 2, (Nrf2) signaling. Treatment with SnPP, a pharmacological inhibitor of HO-1, and knockdown of HO-1 with small interfering RNA (siRNA) restored caspase-3 activity suppressed by gAcrp, indicating a critical role of HO-1 in mediating the protective role of gAcrp in ethanol-induced apoptosis in liver cells. In addition, carbon monoxide, a byproduct obtained from the catabolism of free heme was found to contribute to the anti-apoptotic effect of adiponectin. In conclusion, these data demonstrated that globular adiponectin prevents ethanol-induced apoptosis in HepG2 cells via HO-1 induction and revealed a novel biological response of globular adiponectin in the protection of liver injury from alcohol consumption. ⓒ2012 Elsevier lnc. All rights reserved.

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