کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1931397 1050551 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PPARγ activates ABCA1 gene transcription but reduces the level of ABCA1 protein in HepG2 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
PPARγ activates ABCA1 gene transcription but reduces the level of ABCA1 protein in HepG2 cells
چکیده انگلیسی

Synthesis of ABCA1 protein in liver is necessary for high-density lipoproteins (HDL) formation in mammals. Nuclear receptor PPARγ is known as activator of ABCA1 expression, but details of PPARγ-mediated regulation of ABCA1 at both transcriptional and post-transcriptional levels in hepatocytes have not still been well elucidated. In this study we have shown, that PPARγ activates ABCA1 gene transcription in human hepatoma cells HepG2 through increasing of LXRβ binding with promoter region of ABCA1 gene. Treatment of HepG2 cells with PPARγ agonist GW1929 leads to dissociation of LXRβ from ABCA1/LXRβ complex and to nuclear translocation of this nuclear receptor resulting in reduction of ABCA1 protein level 24 h after treatment. Inhibition of protein kinases MEK1/2 abolishes PPARγ-mediated dissociation of LXRβ from ABCA1/LXRβ complex, but does not block PPARγ-dependent down-regulation of ABCA1 protein in HepG2 cells. These data suggest that PPARγ may be important for regulation of the level of hepatic ABCA1 protein and indicate the new interplays between PPARγ, LXRβ and MEK1/2 in regulation of ABCA1 mRNA and protein expression.

Research highlights
► PPARγ activates ABCA1 gene expression but decreases ABCA1 protein content in human hepatoma cell line HepG2.
► Treatment of HepG2 cells with PPARγ agonist GW1929 leads to dissociation of LXRβ from ABCA1–LXRβ complex.
► Inhibition of protein kinases MEK1/2 abolishes PPARγ-mediated dissociation of LXRβ from ABCA1/LXRβ complex.
► Activation of PPARγ leads to increasing of the level of LXRβ associated with LXRE within ABCA1 gene promoter.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 402, Issue 3, 19 November 2010, Pages 477–482
نویسندگان
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