کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2019925 | 1542249 | 2007 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by atorvastatin is mediated by 15-deoxy-delta-12,14-PGJ2
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Several studies suggested that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) activate peroxisome proliferator-activated receptor-γ (PPAR-γ). Atorvastatin (ATV) increases myocardial levels of prostaglandins (PG) by upregulating and activating cytosolic-phospholipase-A2 and cycloxygenase-2 (COX2). We investigated whether ATV activates PPAR-γ via 15-deoxy-delta-12,14-PGJ2 (15DPGJ2) an endogenous ligand of PPAR-γ and a product of PGD2, and to compare the effects of pioglitazone (PIO), a known direct PPAR-γ activator, to that of ATV. First we measured myocardial 15DPGJ2 levels in the rat heart after a 3-day pretreatment with oral ATV (10 mg/(kg d)), PIO (10 mg/(kg d)), ATV + PIO, ATV + COX1 inhibitor, and ATV + COX2 inhibitor. We also assessed in human umbilical venous endothelial cells (HUVEC) whether ATV and PIO activate PPAR-γ via 15DPGJ2 using siRNA targeted to PGD2 synthase. Both 15DPGJ2 levels and PPAR-γ activation were assessed. ATV and PIO increased myocardial 15DPGJ2 levels in the rat myocardium and HUVEC. siRNA inhibited this increase in both groups. Both ATV and PIO augmented PPAR-γ activation while co-treatment with siRNA completely blocked the ATV effect but only partially inhibited the PIO effect. In conclusion, both ATV and PIO activate PPAR-γ and increase myocardial 15DPGJ2 levels. Activation of PPAR-γ by ATV is mediated solely by 15DPGJ2, whereas PIO activates PPAR-γ both directly and indirectly via 15DPGJ2.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Prostaglandins & Other Lipid Mediators - Volume 84, Issues 1â2, August 2007, Pages 43-53
Journal: Prostaglandins & Other Lipid Mediators - Volume 84, Issues 1â2, August 2007, Pages 43-53
نویسندگان
Yumei Ye, Shawn P. Nishi, Saraswathy Manickavasagam, Yu Lin, Ming-He Huang, J. Regino Perez-Polo, Barry F. Uretsky, Yochai Birnbaum,