European journal of nutrition · 2009
Regulation of expression of apolipoprotein A-I by selenium status in human liver hepatoblastoma cells.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Stahle Jessica A, Vunta Hema, Channa Reddy C, Sandeep Prabhu K
Аннотация
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, 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.
CONCLUSION: 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.
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, 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.
CONCLUSION: 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.