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 journalArticlepeer-review

16 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 Jun

Keywords

  • CHOP
  • ER STRESS
  • HEPATIC STEATOSIS
  • HIF-1α
  • LIPOAPOPTOSIS
  • NON-ALCOHOLIC FATTY LIVER DISEASE

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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