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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 1 2009

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Hepatoblastoma
Apolipoprotein A-I
Selenium
Peroxisome Proliferator-Activated Receptors
Liver
HDL Lipoproteins
Hepatocytes
Oxidative Stress
Sodium Selenite
Total Parenteral Nutrition
Hep G2 Cells
Cytoplasmic and Nuclear Receptors
Luciferases
Cardiomyopathies
Immunoprecipitation
Coronary Disease
Lipopolysaccharides
Transcription Factors
Cell Culture Techniques
Western Blotting

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

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title = "Regulation of expression of apolipoprotein A-I by selenium status in human liver hepatoblastoma cells",
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.",
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Regulation of expression of apolipoprotein A-I by selenium status in human liver hepatoblastoma cells. / Stahle, Jessica A.; Vunta, Hema; Reddy, C. Channa; Prabhu, Kumble Sandeep.

In: European Journal of Nutrition, Vol. 48, No. 5, 01.08.2009, p. 283-290.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Regulation of expression of apolipoprotein A-I by selenium status in human liver hepatoblastoma cells

AU - Stahle, Jessica A.

AU - Vunta, Hema

AU - Reddy, C. Channa

AU - Prabhu, Kumble Sandeep

PY - 2009/8/1

Y1 - 2009/8/1

N2 - 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.

AB - 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.

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