Journal
EXPERIMENTAL EYE RESEARCH
Volume 84, Issue 5, Pages 886-893Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2007.01.009
Keywords
fenofibrate; human retinal endothelial cells; apoptosis; AMP-activated protein kinase; vascular endothelial growth factor
Categories
Ask authors/readers for more resources
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 alpha (PPAR alpha) antagonist MK 886, and selective agonist for PPAR alpha, 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 PPAR alpha-independent, but AMPK-dependent pathway. Thus fenofibrate may have a novel therapeutic property that can control unwanted cell death found in diabetic retinopathy. (C) 2007 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available