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

Title
Globular adiponectin inhibits ethanol-induced apoptosis in HepG2 cells through heme oxygenase-1 induction
Author(s)
사로즈네팔김미진수베디아미트이응석용철순김정애강원구박필훈곽미경[곽미경]Dharamvir [Dharamvir ]
Keywords
ACTIVATED PROTEIN-KINASE; ALCOHOLIC FATTY LIVER; MOLECULAR-MECHANISMS; HORMONE ADIPONECTIN; INSULIN-RESISTANCE; ENDOTHELIAL-CELLS; TERMINAL KINASE; TNF-ALPHA; EXPRESSION; PATHWAY
Issue Date
201210
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
BIOCHEMICAL PHARMACOLOGY, v.84, no.7, pp.974 - 983
Abstract
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 globular adiponectin (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 antiapoptotic 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. (C) 2012 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/27160http://dx.doi.org/10.1016/j.bcp.2012.07.019
ISSN
0006-2952
Appears in Collections:
중앙도서관 > rims journal
약학대학 > 약학부 > Articles
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