HIF-1α expression as a protective strategy of HepG2 cells against fatty acid-induced toxicity

Wonbaek Yoo, Kyung Hee Noh, Jae Hee Ahn, Ji Hee Yu, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei-Hyun Baik, Dong Seop Choi, Tae Woo Kim, Hyo Joon Kim, Nan Hee Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 1α (HIF-1α) in this process has been suggested, but direct evidence is lacking. Here, we used HepG2 cells as a model to study whether HIF-1α can reduce palmitic acid-induced lipotoxicity and ER stress. In HepG2 cells treated with 500 μM palmitic acid, HIF-1α expression increased transiently, the decline was associated with increased cleaved caspase-3 expression. Overexpression and knockdown of HIF-1α 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-1α binding to the CHOP promoter hypoxia response element. These results indicate that hepatocyte lipotoxicity is associated with decreased HIF-1α expression. It also suggests that upregulation of HIF-1α can be a possible strategy to reduce lipotoxicity in non-alcoholic fatty liver disease.

Original languageEnglish
Pages (from-to)1147-1158
Number of pages12
JournalJournal of Cellular Biochemistry
Volume115
Issue number6
DOIs
Publication statusPublished - 2014 Jan 1

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Hypoxia-Inducible Factor 1
Hep G2 Cells
Toxicity
Transcription Factor CHOP
Fatty Acids
Endoplasmic Reticulum Stress
Palmitic Acid
Hepatocytes
Up-Regulation
Response Elements
Fatty Liver
Nonesterified Fatty Acids
Caspase 3
Liver
Apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

HIF-1α expression as a protective strategy of HepG2 cells against fatty acid-induced toxicity. / 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.

In: Journal of Cellular Biochemistry, Vol. 115, No. 6, 01.01.2014, p. 1147-1158.

Research output: Contribution to journalArticle

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