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


OBJECTIVE
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, PPARalpha, was trans-repressed by the presence of the oxidative stress-responsive transcription factor, NF-kappaB.


METHODS
Modulation of expression of apoA-I and activation of nuclear NF-kappaB subunit p65 and PPARalpha by Se status were evaluated by Western blot and luciferase-based assays. Interaction of p65 with PPARalpha 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 PPARalpha to modulate apoA-I transcription.


CONCLUSIONS
Our results suggest that supplementation of hepatocytes with Se mitigates oxidative stress-dependent repression of apoA-I expression by suppressing the NF-kappaB pathway, which allows PPARalpha to effectively drive the expression of apoA-I.
Stahle
Jessica A
JA
Undergraduate Program in Animal Biosciences, The Pennsylvania State University, University Park, PA, 16802 USA.
Vunta
Hema
H
Channa Reddy
C
C
Sandeep Prabhu
K
K
D000818:Animals; D016632:Apolipoprotein A-I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology*; D051996:Transcription Factor RelA
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D016328:NF-kappa B; D047493:PPAR alpha; D051996:Transcription Factor RelA; D012643:Selenium