کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1910112 1046753 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oxidative stress modulates PPARγ in vascular endothelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Oxidative stress modulates PPARγ in vascular endothelial cells
چکیده انگلیسی

The peroxisome proliferator-activated receptor γ (PPARγ) plays an important role in vascular regulation. However, the impact of oxidative stress on PPARγ expression and activity has not been clearly defined. Human umbilical vein endothelial cells (HUVECs) were exposed to graded concentrations of H2O2 for 0.5–72 h, or bovine aortic endothelial cells (BAECs) were exposed to alterations in extracellular thiol/disulfide redox potential (Eh) of the cysteine/cystine couple. Within 2 h, H2O2 reduced HUVEC PPARγ mRNA and activity and reduced the expression of two PPARγ-regulated genes without altering PPARγ protein levels. After 4 h H2O2 exposure, mRNA levels remained reduced, whereas PPARγ activity returned to control levels. PPARγ mRNA levels remained depressed for up to 72 h after exposure to H2O2, without any change in PPARγ activity. Catalase prevented H2O2-induced reductions in PPARγ mRNA and activity. H2O2 (1) reduced luciferase expression in HUVECs transiently transfected with a human PPARγ promoter reporter, (2) failed to alter PPARγ mRNA half-life, and (3) transiently increased expression and activity of c-Fos and phospho-c-Jun. Treatment with the AP1 inhibitor curcumin prevented H2O2-mediated reductions in PPARγ expression. In addition, medium having an oxidized Eh reduced BAEC PPARγ mRNA and activity. These findings demonstrate that oxidative stress, potentially through activation of inhibitory redox-regulated transcription factors, attenuates PPARγ expression and activity in vascular endothelial cells through suppression of PPARγ transcription.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 48, Issue 12, 15 June 2010, Pages 1618–1625
نویسندگان
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