کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4012907 | 1261219 | 2007 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway](/preview/png/4012907.png)
Fenofibrate, a widely used hypolipidemic drug, has anti-inflammatory and anti-atherosclerotic effects in the vessel wall. In the present study, we report an anti-apoptotic property of fenofibrate in human retinal endothelial cells (HRECs) and describe an underlying molecular mechanism. Treatment with fenofibrate protected HRECs from apoptosis in response to serum deprivation in a dose-dependent manner. This inhibition of apoptosis by fenofibrate was not altered by peroxisome proliferator-activated receptor α (PPARα) antagonist MK 886, and selective agonist for PPARα, WY-14643 had no beneficial effects on serum deprivation-induced cell death. Fenofibrate potently induced a sustained activation of AMP-activated protein kinase (AMPK) and vascular endothelial growth factor (VEGF) mRNA expression. Furthermore, compound C, a specific AMPK inhibitor, almost completely blocked the fenofibrate-induced survival effect as well as VEGF mRNA expression. Taken together, these results suggest that fenofibrate prevents apoptotic cell death induced by serum deprivation through PPARα-independent, but AMPK-dependent pathway. Thus fenofibrate may have a novel therapeutic property that can control unwanted cell death found in diabetic retinopathy.
Journal: Experimental Eye Research - Volume 84, Issue 5, May 2007, Pages 886–893