Diabetes Metab J > Volume 30(3); 2006 > Article
Korean Diabetes Journal 2006;30(3):151-160.
DOI: https://doi.org/10.4093/jkda.2006.30.3.151    Published online May 1, 2006.
Protective Effect of PGC-1 on Lipid Overload-induced Apoptosis in Vascular Endothelial Cell.
Eun Hee Koh, Youn Mi Kim, Ha Jung Kim, Woo Je Lee, Jong Chul Won, Min Seon Kim, Ki Up Lee, Joong Yeol Park
1Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Korea.
2Asan Institute for Life Sciences, University of Ulsan College of Medicine, Korea.
Abstract
BACKGROUND
Fatty acids contribute to endothelial cell dysfunction and apoptosis by inducing accumulation of long chain fatty acyl CoA (LCAC), which increases oxidative stress in vascular endothelial cells. Forced expression of PGC-1 was shown to induce mitochondrial biogenesis and to control expression of mitochondrial enzymes involved in fatty acid oxidation. This study was undertaken to test the hypothesis that PGC-1 overexpression could prevent endothelial cell apoptosis by enhancing fatty acid oxidation and relieving oxidative stress in vascular endothelium. METHODS: Adenoviruses containing human PGC-1 (Ad-PGC-1) and beta-galactosidase (Ad-beta-gal) were transfected to confluent human aortic endothelial cells (HAECs). To investigate the effect of adenoviral PGC-1 gene transfer on apoptosis, combined treatment of linoleic acid (LA), an unsaturated fatty acid, was performed. RESULTS: PGC-1 overexpression inhibited the increase in ROS production and apoptosis of HAECs induced by LA. Also, PGC-1 led to a significant increase in fatty acid oxidation and decrease in triglyceride content in HAECs. LA caused the decrease of adenine nucleotide translocase (ANT) activity and transient mitochondrial hyperpolarization, which was followed by depolarization. PGC-1 overexpression prevented these processes. CONCLUSION: In summary, PGC-1 overexpression inhibited mitochondrial dysfunction and apoptosis by facilitating fatty acid oxidation and protecting against the damage from oxidative stress in HAECs. The data collectively suggest that the regulation of intracellular PGC-1 expression might play a critical role in preventing atherosclerosis.
Key Words: Apoptosis, Atherosclerosis, Human aortic endothelial cells, Mitochondria, Oxidative stress, PGC-1


ABOUT
BROWSE ARTICLES
FOR CONTRIBUTORS
Editorial Office
101-2104, Lotte Castle President, 109 Mapo-daero, Mapo-gu, Seoul 04146, Korea​
Tel: +82-2-714-9064    Fax: +82-2-714-9084    E-mail: diabetes@kams.or.kr                

Copyright © 2021 by Korean Diabetes Association.

Developed in M2PI

Close layer