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Hemeoxygenase-1 expression in response to arecoline-induced oxidative stress in human umbilical vein endothelial cells.
MedLine Citation:
PMID:  21889036     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Arecoline, the most abundant areca alkaloid, has been reported to stimulate reactive oxygen species (ROS) production in several cell types. Overproduction of ROS has been implicated in atherogenesis. Hemeoxygenase-1 (HO-1) has cytoprotective activities in vascular tissues. This study investigated the effect of arecoline on adhesion molecule expression and explored the role of HO-1 in this process.
METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with arecoline, then ROS levels and the expression of adhesion molecules and HO-1 were analyzed and potential signaling pathways investigated.
RESULTS: After 2h of arecoline treatment, ROS production was stimulated and reached a maximum at 12h. Expression of the adhesion molecules ICAM and VCAM was also induced. Glutathione pretreatment completely blocked arecoline-stimulated ROS production and VCAM expression, but not ICAM expression. Arecoline also induced HO-1 expression and this effect was partly due by ROS stimulation. Inhibition of c-jun N-terminal kinase (JNK) by SP600125, p38 by SB 203580, or tyrosine kinase by genistein reduced arecoline-induced HO-1 expression. In contrast, inhibition of ERK (extracellular signal-related MAP kinase) by PD98059 had no effect. Transfection of HUVECs with the GFP/HO-1 gene, which resulted in a 5-fold increase in HO-1 activity, markedly, but not completely, inhibited the decrease in cell viability caused by arecoline.
CONCLUSIONS: This study demonstrates that, in HUVECs, arecoline stimulates ROS production and ICAM and VCAM expression. HO-1 expression is also upregulated through the ROS, tyrosine kinase, and MAPK (JNK and p38) signaling pathways.
Authors:
Thu-Ching Hung; Li-Wen Huang; Shu-Jem Su; Bau-Shan Hsieh; Hsiao-Ling Cheng; Yu-Chen Hu; Yen-Hui Chen; Chi-Ching Hwang; Kee-Lung Chang
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Publication Detail:
Type:  Journal Article     Date:  2010-06-17
Journal Detail:
Title:  International journal of cardiology     Volume:  151     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  187-94     Citation Subset:  IM    
Copyright Information:
Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
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