کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2553370 1560755 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PPARα activators upregulate eNOS activity and inhibit cytokine-induced NF-κB activation through AMP-activated protein kinase activation
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
PPARα activators upregulate eNOS activity and inhibit cytokine-induced NF-κB activation through AMP-activated protein kinase activation
چکیده انگلیسی

Endothelium-derived NO is an important mediator of vascular protection and adhesion molecule expression on the endothelial cell surface is critical for leukocyte recruitment to atherosclerotic lesions. We hypothesized that AMP-activated protein kinase (AMPK) activity is a down-stream mediator of the beneficial effects of PPARα activators on vascular endothelial cells. Treatment of human umbilical vein endothelial cells (HUVEC) with fenofibrate or WY14643 resulted in transient activation of AMPK, as monitored by phosphorylation of AMPK and its down-stream target, acetyl-CoA carboxylase. Fenofibrate caused phosphorylation of Akt and eNOS, leading to increased production of NO, and also caused inhibition of cytokine-induced NF-κB activation, leading to suppression of expression of adhesion molecule genes. Significant decreases in eNOS activity and NO production in response to fenofibrate were observed in cells treated with AMPK siRNA or with AraA, a pharmacological inhibitor of AMPK. The attenuation of fenofibrate-induced inhibition of NF-κB activation was observed in mouse endothelial (SVEC4) cells treated with AMPK siRNA or with AraA. We demonstrated that TNFα stimulates IκB-α phosphorylation through induction of IKK activity, and that fenofibrate inhibits IKK activity and TNFα-induced IκB-α phosphorylation. Our findings suggest that the beneficial effects of PPARα activators on endothelial cells such as inhibition of diabetic microangiopathy might be attributed to the induction of AMPK activation beyond its lipid-lowering actions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 82, Issues 15–16, 9 April 2008, Pages 884–891
نویسندگان
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