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KMID : 0354720070310030200
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Journal of Korean Diabetes Association
2007 Volume.31 No. 3 p.200 ~ p.207
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The Effect of Alpha-Lipoic Acid on the Cell Cycle Arrest and Apoptosis in Rat Vascular Smooth Muscle Cells
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Kim Hey-Jin
Lee In-Kyu
Kim Young-Ho
Shin Soon-Young
Lee Young-Han
Kim Jung-Guk
Kim Bo-Wan
Kim Hye-Sun
Kim Mi-Kyung
Park Keun-Gyu
Ryu Seong-Yeol
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Abstract
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Background: The proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of atheroscelrosis and
post-angioplasty restenosis. We previously showed that alpha-lipoic acid (ALA) inhibited neointimal hyperplasia and has potential anti-atherosclerosis effect in rat carotid artery balloon injured model. Here, we investigated whether alpha-lipoic acid inhibited proliferation of cells and induced apoptosis in rat vascular smooth muscle cells.
Methods: VSMCs were treated with ALA under each condition, harvested and protein was extracted. Same
amount of protein was loaded into SDS-PAGE and western blot analysis was performed with various cell cycle regulation protein. To examine ALA induce apoptosis in VSMCs, FACS and DNA fragmentation assay were performed. Antioxidant effect of ALA was determined by DCF-DA staining.
Results: ALA induced VSMCs cell cycle arrest and induced p21, p27 and p53 proteins. Also ALA induced PTEN expression and AMPK phosphorylation. Increased AMPK phosphorylation reduced Erk-2 phosphorylation and finally arrested cell cycle promotion. The apoptotic effect was also shown by ALA treatment. Also we confirmed that ALA reduced ROS generation in VSMCs.
Conclusion: The present data suggest that ALA has anti-proliferative effect and arrests cell proliferation.
Therefore, ALA may provide new strategies for the prevention of neointimal hyperplasia after angioplasty.
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KEYWORD
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Alpha Lipoic acid, vascular smooth muscle cell, cell cycle, apoptosis
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