Liver receptor homolog-1 regulates mouse superoxide dismutase 2

Jun Su Lee, Sijeong Bae, Hye Suk Kang, Seung Soon Im, Young Ah Moon

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Liver receptor homolog-1 (LRH-1) is a nuclear receptor that plays an important role in the regulation of bile acid biosynthesis, cholesterol reverse transport, steroidogenesis, and exocrine pancreatic enzyme production. In the current study, previously published data from a genome wide analysis of LRH-1 binding in the liver were re-analyzed to identify new LRH-1 targets and propose new roles for LRH-1 in the liver. Superoxide dismutase 2 (Sod2) was identified, which contains putative LRH-1 binding sites in the proximal promoter. When hepatocytes were treated with the LRH-1 agonist RJW101, Sod2 expression was dramatically increased and reactive oxygen species (ROS) production, which was induced by a high concentration of palmitate, was significantly reduced. A LRH-1 binding site was mapped to −288/−283 in the Sod2 promoter, which increased Sod2 promoter activity in response to LRH-1 and its agonist. LRH-1 binding to this site was confirmed using a chromatin immunoprecipitation assay. These results suggest that Sod2 is a target gene of LRH-1, and that LRH-1 agonists can mediate a reduction in ROS production and oxidative stress driven by an excess of fatty acids, as exhibited in nonalcoholic fatty liver disease.

Original languageEnglish (US)
Pages (from-to)299-304
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume489
Issue number3
DOIs
StatePublished - Jul 29 2017

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Keywords

  • Liver receptor homolog-1
  • Nonalcoholic fatty liver disease
  • Reactive oxygen species
  • Superoxide dismutase 2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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