HIF-1 alpha Expression as a Protective Strategy of HepG2 Cells Against Fatty Acid-Induced Toxicity
- Authors
- Yoo, Wonbaek; Noh, Kyung Hee; Ahn, Jae Hee; Yu, Ji Hee; Seo, Ji A.; Kim, Sin Gon; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop; Kim, Tae Woo; Kim, Hyo Joon; Kim, Nan Hee
- Issue Date
- 6월-2014
- Publisher
- WILEY
- Keywords
- NON-ALCOHOLIC FATTY LIVER DISEASE; HEPATIC STEATOSIS; LIPOAPOPTOSIS; ER STRESS; HIF-1; CHOP
- Citation
- JOURNAL OF CELLULAR BIOCHEMISTRY, v.115, no.6, pp.1147 - 1158
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CELLULAR BIOCHEMISTRY
- Volume
- 115
- Number
- 6
- Start Page
- 1147
- End Page
- 1158
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/98281
- DOI
- 10.1002/jcb.24757
- ISSN
- 0730-2312
- Abstract
- Free fatty acid-induced lipotoxicity via increased endoplasmic reticulum (ER) stress and hepatocyte apoptosis is a key pathological mechanism of non-alcoholic steatohepatitis. A role of hypoxia-inducible factor 1 (HIF-1) in this process has been suggested, but direct evidence is lacking. Here, we used HepG2 cells as a model to study whether HIF-1 can reduce palmitic acid-induced lipotoxicity and ER stress. In HepG2 cells treated with 500 mu M palmitic acid, HIF-1 expression increased transiently, the decline was associated with increased cleaved caspase-3 expression. Overexpression and knockdown of HIF-1 decreased and exacerbated, respectively, palmitic acid-induced lipoapoptosis. The overexpression also blunted upregulation of the ER stress markers, C/EBP homologous protein (CHOP) and chaperone immunoglobulin heavy chain binding protein (Bip), while the knockdown increased the level of CHOP. In line with this, CHOP promoter activity decreased following HIF-1 binding to the CHOP promoter hypoxia response element. These results indicate that hepatocyte lipotoxicity is associated with decreased HIF-1 expression. It also suggests that upregulation of HIF-1 can be a possible strategy to reduce lipotoxicity in non-alcoholic fatty liver disease. J. Cell. Biochem. 115: 1147-1158, 2014. (c) 2014 Wiley Periodicals, Inc.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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