RRC ID 197
Author Xu JW, Ikeda K, Kobayakawa A, Ikami T, Kayano Y, Mitani T, Yamori Y.
Title Downregulation of Rac1 activation by caffeic acid in aortic smooth muscle cells.
Journal Life Sci.
Abstract 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.
Volume 76(24)
Pages 2861-72
Published 2005-4-29
DOI 10.1016/j.lfs.2004.11.015
PII S0024-3205(05)00073-1
PMID 15808886
MeSH 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 Muscle, Smooth, Vascular / 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*
IF 3.234
Times Cited 16
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY
Resource
Rats SHRSP/Izm(strainID=409) WKY/Izm(strainID=412)