title: Modulation of Atg5 expression by globular adiponectin contributes to autophagy flux and suppression of ethanol-induced cell death in liver cells.
abstract: Globular adiponectin (gAcrp) protects liver cells from ethanol-induced apoptosis via induction of autophagy. However, the underlying mechanisms are unknown. The present study aims to investigate the potential role of autophagy-related protein 5 (Atg5), an essential Atg for the elongation of autophagosomes, in suppression of ethanol-induced cytotoxicity by gAcrp. Here, we demonstrated that suppression of Atg5 expression by ethanol was restored by pretreatment with gAcrp both in primary rat hepatocytes and human hepatoma cell line (HepG2). Moreover, ethanol-induced accumulation of p62 (sequestosome1), a marker of autophagic flux, was restored by gAcrp treatment, implying that gAcrp modulates autophagic flux in liver cells. Further, Atg5 silencing prevented p62 degradation by gAcrp, suggesting that Atg5 plays a critical role in induction of autophagic flux by gAcrp. Interestingly, gene silencing of Atg5 by siRNA abrogated restoration of autophagosome formation by gAcrp in ethanol-treated cells. Finally, protection of liver cells by gAcrp from ethanol-induced apoptosis was also significantly attenuated by knocking-down of Atg5 expression, suggesting an important role of Atg5 in autophagy induction and cellular apoptosis modulated by gAcrp. Taken together, our data demonstrated that Atg5 expression, at least in part, is implicated in gAcrp-induced autophagy and subsequent anti-apoptotic effects in ethanol-treated liver cells.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsanbuk-do 712-749, Republic of Korea.
authors.forename: Saroj
authors.initials: S
authors.lastname: Nepal
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsanbuk-do 712-749, Republic of Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsanbuk-do 712-749, Republic of Korea.
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsanbuk-do 712-749, Republic of Korea.
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsanbuk-do 712-749, Republic of Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Wonkwang University, Chonbuk 570-749, Republic of Korea.
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Sohn
authors.affiliation: College of Pharmacy, Wonkwang University, Chonbuk 570-749, Republic of Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Wonkwang University, Chonbuk 570-749, Republic of Korea.
authors.forename: Kyung
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsanbuk-do 712-749, Republic of Korea. Electronic address: taecheon@yu.ac.kr.
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsanbuk-do 712-749, Republic of Korea. Electronic address: parkp@yu.ac.kr.
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: C502778:ATG5 protein, human; D052242:Adiponectin; C545865:Atg5 protein, rat; D000071187:Autophagy-Related Protein 5; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008869:Microtubule-Associated Proteins; D011506:Proteins; D000431:Ethanol; D055372:AMP-Activated Protein Kinases; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Adiponectin; Apoptosis; Atg5; Autophagy; Ethanol