Activation of autophagy by globular adiponectin attenuates ethanol-induced apoptosis in HepG2 cells: Involvement of AMPK/FoxO3A axis

Title
Activation of autophagy by globular adiponectin attenuates ethanol-induced apoptosis in HepG2 cells: Involvement of AMPK/FoxO3A axis
Author(s)
박필훈사로즈 네팔[사로즈 네팔]
Keywords
ALCOHOLIC LIVER-DISEASE; PROTEIN-KINASE; FATTY LIVER; RAT HEPATOCYTES; HEPATOCELLULAR-CARCINOMA; DEATH; CANCER; INJURY; CROSSTALK; MECHANISM
Issue Date
201310
Publisher
ELSEVIER SCIENCE BV
Citation
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v.1833, no.10, pp.2111 - 2125
Abstract
Hepatocellular apoptosis is an important pathological entity of alcoholic liver disease. Previously, we have shown that globular adiponectin (gAcrp) protects liver cells from ethanol-induced apoptosis by modulating an array of signaling pathways. In the present study, we investigated the role of autophagy induction by gAcrp in the suppression of ethanol-induced apoptosis and its potential mechanism(s) in liver cells. Here, we demonstrated that gAcrp significantly restores ethanol-induced suppression of autophagy-related genes, including Beclin-1 and microtubule-associated protein light chain (LC3B) both in primary rat hepatocytes and human hepatoma cell line (HepG2). Globular adiponectin also restored autophagosome formation suppressed by ethanol treatment in HepG2. Furthermore, inhibition of gAcrp-induced autophagic process by knock-down of LOB prevented protection from ethanol-induced apoptosis. In particular, the autophagic process induced by gAcrp was involved in the suppression of ethanol-induced activation of caspase-8 and expression of Bax. Moreover, knock-down of AMPK by small interfering RNA (siRNA) blocked gAcrp-induced expression of genes related to autophagy, which in turn prevented protection from ethanol-induced apoptosis, suggesting that AMPK plays an important role in the induction of autophagy and protection of liver cells by gAcrp. Finally, we also showed that gAcrp treatment induces translocation of the forkhead box 0 member protein, FoxO3A, into the nucleus, which may play a role in the induction of autophagy-related genes. Taken together, our data demonstrated that gAcrp protects liver cells from ethanol-induced apoptosis via induction of autophagy. Further, the AMPK-FoxO3A axis plays a cardinal role in gAcrp-induced autophagy and subsequent inhibition of ethanol-induced apoptosis. (C) 2013 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/28805http://dx.doi.org/10.1016/j.bbamcr.2013.05.013
ISSN
0167-4889
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약학대학 > 약학부 > Articles
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