Regulation of expression of apolipoprotein A-I by selenium status in human liver hepatoblastoma cells

Jessica A. Stahle, Hema Vunta, C. Channa Reddy, K. Sandeep Prabhu

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: Cardiomyopathy is common to areas with low selenium (Se) intake and in patients receiving total parenteral nutrition. Although controversial, a few studies have suggested a protective role for Se in coronary heart disease on the basis of modulation of high-density lipoproteins (HDL). Aims of the study: In this study, the role of Se as a positive regulator of expression of a key HDL, apolipoprotein A-I (apoA-I), has been evaluated in human hepatoblastoma (HepG2) cell culture model. We further examined if the transcription of apoA-I, driven by the nuclear hormone receptor, peroxisome-proliferator activated receptor, PPARα, was trans-repressed by the presence of the oxidative stress-responsive transcription factor, NF-κB. Methods: Modulation of expression of apoA-I and activation of nuclear NF-κB subunit p65 and PPARα by Se status were evaluated by Western blot and luciferase-based assays. Interaction of p65 with PPARα was evaluated by immunoprecipitation. Results: HepG2 cultured in media with Se (100 nM) demonstrated an increase in the expression of apoA-I when compared to Se-deficient cells. A similar trend was also seen in mice that were supplemented with 0.4 ppm of Se as sodium selenite. Treatment of Se-supplemented cells with bacterial lipopolysaccharide (LPS) showed induction of apoA-I. Supplementation of hepatocytes with Se decreased the nuclear levels of p65, which prevented its interaction with PPARα to modulate apoA-I transcription. Conclusion: Our results suggest that supplementation of hepatocytes with Se mitigates oxidative stress-dependent repression of apoA-I expression by suppressing the NF-κB pathway, which allows PPARα to effectively drive the expression of apoA-I.

Original languageEnglish (US)
Pages (from-to)283-290
Number of pages8
JournalEuropean Journal of Nutrition
Volume48
Issue number5
DOIs
StatePublished - Aug 2009

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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