Document Detail


Superoxide is a potential culprit of caspase-3 dependent endothelial cell death induced by lysophosphatidylcholine.
MedLine Citation:
PMID:  20814064     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Oxidative stress in the vascular wall has intimately been implicated in the apoptosis of human umbilical vein endothelial cells (HUVECs) by lysophosphatidylcholine (LPC). However, the major type of reactive oxygen species (ROS) in this apoptotic signaling pathway remains to be clarified. In this study, we report that superoxide mediate LPC-induced caspase-3 dependent apoptosis in cultured HUVECs. The stimulation of HUVECs with LPC evoked apoptosis and ROS generation, and inhibited nitric oxide (NO) production in a dose-dependent manner. The classical caspase-3 dependent apoptosis was determined after 16 hours treatment by Western blotting using an antibody against cleaved caspase-3. The caspase-3 activation induced by LPC was prominently inhibited by antioxidants or NO donors and enhanced by NO inhibitors. Especially, LPC-induced caspase-3 activation was inhibited by superoxide dismutase (SOD) and enhanced by ammonium tetrathiomolybdate, SOD inhibitor. Additionally, xanthine/xanthine oxidase mixture increased the caspase-3 activation but catalase failed to reduce this superoxide-induced caspase-3 activation. These findings indicate that the superoxide generation caused by LPC activates the caspase-3 which results in HUVECs death. This study reveals some evidences linking superoxide with caspase-3 activation and provides a new dimension to superoxide-mediated caspase-3 activation in developing the endothelial dysfunction and atherosclerosis.
Authors:
S Park; J A Kim; S Choi; S H Suh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of physiology and pharmacology : an official journal of the Polish Physiological Society     Volume:  61     ISSN:  1899-1505     ISO Abbreviation:  J. Physiol. Pharmacol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-09-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9114501     Medline TA:  J Physiol Pharmacol     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  375-81     Citation Subset:  IM    
Affiliation:
Department of Physiology and Medical Research Center, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
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