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Exp Eye Res. 2007 May;84(5):886-93. Epub 2007 Jan 27.

Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway.

Author information

1
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, 224-1 Heuk Seok-dong, Dongjak-ku, Seoul 156-755, South Korea. jtkim@cau.ac.kr

Abstract

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 (PPARalpha) antagonist MK 886, and selective agonist for PPARalpha, 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 PPARalpha-independent, but AMPK-dependent pathway. Thus fenofibrate may have a novel therapeutic property that can control unwanted cell death found in diabetic retinopathy.

PMID:
17343853
DOI:
10.1016/j.exer.2007.01.009
[Indexed for MEDLINE]

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