Document Detail


Downregulation of Rac1 activation by caffeic acid in aortic smooth muscle cells.
MedLine Citation:
PMID:  15808886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Caffeic acid, a dietary phenol from coffee, fruits and vegetables, is an efficient antioxidant. However, little is known about its anti-oxidative mechanism in the modulation of fundamental cellular processes. In this study, we investigated whether caffeic acid regulates Rac1 GTPase activity, a partner of NADPH oxidase. Our results showed that caffeic acid decrease Rac1 protein level under basal conditions and incubation with angiotensin II (ANG II) in vascular smooth muscle cells. In a Rac-bound-to-PAK pull down assay, caffeic acid clearly inhibited Rac1 activity. We also observed that caffeic acid suppressed the generation of superoxide anion stimulated by ANG II that activates NADPH oxidase. On the other hand, co-incubation with caffei caid and cycloheximide significantly accelerated the Rac1 degradation. In addition, pretreatment with caffeic acid for 24 hours was able to prevent phosphorylation of MLC and HSP27, when cells were challenged with ANG II through the redox sensitive pathway. These results support the hypothesis that caffeic acid reduces Rac1 GTPase protein and activity level, followed by a down-regulation of NADPH oxidase activity.
Authors:
Jin-Wen Xu; Katsumi Ikeda; Akira Kobayakawa; Takao Ikami; Yasuyo Kayano; Takahiko Mitani; Yukio Yamori
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  76     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-05     Completed Date:  2005-05-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2861-72     Citation Subset:  IM    
Affiliation:
Frontier Health Science, School of Human Environmental Science, MUKOGAWA Women's University, Nishinomiya, Hyogo, 663-8179, Japan. jwxu@mwu.mukogawa-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Angiotensin II / metabolism
Animals
Antioxidants / pharmacology*
Aorta / cytology*
Blotting, Western
Caffeic Acids / pharmacology*
Cycloheximide / metabolism
Enzyme Activation / drug effects
HSP27 Heat-Shock Proteins
Heat-Shock Proteins / metabolism
Male
Muscle, Smooth, Vascular / cytology,  metabolism*
Neoplasm Proteins / metabolism
Phosphorylation / drug effects
Protein-Serine-Threonine Kinases
Rats
Rats, Inbred WKY
Superoxides / metabolism
Transfection
p21-Activated Kinases
rac1 GTP-Binding Protein / metabolism*
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Caffeic Acids; 0/HSP27 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Hspb1 protein, rat; 0/Neoplasm Proteins; 11062-77-4/Superoxides; 11128-99-7/Angiotensin II; 331-39-5/caffeic acid; 66-81-9/Cycloheximide; EC 2.7.11.1/Pak1 protein, rat; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/p21-Activated Kinases; EC 3.6.1.-/Rac1 protein, rat; EC 3.6.5.2/rac1 GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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