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

Jaetaek Kim; Ji Hyun Ahn; Jeong Hun Kim; Young Suk Yu; Ho Shik Kim; Joohun Ha; Soon Hyun Shinn; Yeon Sahng Oh

doi:10.1016/j.exer.2007.01.009

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

Jaetaek Kim
, Ji Hyun Ahn
, Jeong Hun Kim
, Young Suk Yu
, Ho Shik Kim
, Joohun Ha
, Soon Hyun Shinn
, Yeon Sahng Oh

Department of Biochemistry

College of Medicine
Seoul National University
College of Medicine

Research output: Contribution to journal › Article › peer-review

107 Scopus citations

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 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.

Original language	English
Pages (from-to)	886-893
Number of pages	8
Journal	Experimental Eye Research
Volume	84
Issue number	5
DOIs	https://doi.org/10.1016/j.exer.2007.01.009
State	Published - May 2007

Bibliographical note

Funding Information:
We thank Professor E. Dale Abel and Dr. Adam R. Wende of the School of Medicine, University of Utah for critically reading the manuscript, and Dr. Jeong-Ki Min of the Department of Biochemistry College of Sciences, Yonsei University for very helpful discussion and advice. This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2005-003-E00104).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

AMP-activated protein kinase
apoptosis
fenofibrate
human retinal endothelial cells
vascular endothelial growth factor

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10.1016/j.exer.2007.01.009

Cite this

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title = "Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway",

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 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.",

keywords = "AMP-activated protein kinase, apoptosis, fenofibrate, human retinal endothelial cells, vascular endothelial growth factor",

author = "Jaetaek Kim and Ahn, \{Ji Hyun\} and Kim, \{Jeong Hun\} and Yu, \{Young Suk\} and Kim, \{Ho Shik\} and Joohun Ha and Shinn, \{Soon Hyun\} and Oh, \{Yeon Sahng\}",

note = "Funding Information: We thank Professor E. Dale Abel and Dr. Adam R. Wende of the School of Medicine, University of Utah for critically reading the manuscript, and Dr. Jeong-Ki Min of the Department of Biochemistry College of Sciences, Yonsei University for very helpful discussion and advice. This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2005-003-E00104).",

year = "2007",

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doi = "10.1016/j.exer.2007.01.009",

language = "English",

volume = "84",

pages = "886--893",

journal = "Experimental Eye Research",

issn = "0014-4835",

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T1 - Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway

AU - Kim, Jaetaek

AU - Ahn, Ji Hyun

AU - Kim, Jeong Hun

AU - Yu, Young Suk

AU - Kim, Ho Shik

AU - Ha, Joohun

AU - Shinn, Soon Hyun

AU - Oh, Yeon Sahng

N1 - Funding Information: We thank Professor E. Dale Abel and Dr. Adam R. Wende of the School of Medicine, University of Utah for critically reading the manuscript, and Dr. Jeong-Ki Min of the Department of Biochemistry College of Sciences, Yonsei University for very helpful discussion and advice. This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2005-003-E00104).

PY - 2007/5

Y1 - 2007/5

N2 - 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.

AB - 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.

KW - AMP-activated protein kinase

KW - apoptosis

KW - fenofibrate

KW - human retinal endothelial cells

KW - vascular endothelial growth factor

UR - https://www.scopus.com/pages/publications/34247108235

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M3 - Article

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AN - SCOPUS:34247108235

SN - 0014-4835

VL - 84

SP - 886

EP - 893

JO - Experimental Eye Research

JF - Experimental Eye Research

IS - 5

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

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