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Resveratrol inhibits collagen-induced platelet stimulation through suppressing NADPH oxidase and oxidative inactivation of SH2 domain-containing protein tyrosine phosphatase-2

Title
Resveratrol inhibits collagen-induced platelet stimulation through suppressing NADPH oxidase and oxidative inactivation of SH2 domain-containing protein tyrosine phosphatase-2
Authors
Jang, Ji YongMin, Ji HyunWang, Su BinChae, Yun HeeBaek, Jin YoungKim, MyungheeRyu, Jae-SangChang, Tong-Shin
Ewha Authors
창동신류재상
SCOPUS Author ID
창동신scopus; 류재상scopus
Issue Date
2015
Journal Title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN
0891-5849JCR Link1873-4596JCR Link
Citation
vol. 89, pp. 842 - 851
Keywords
ResveratrolAntiplateletReactive oxygen speciesNADPH oxidaseSH-2 domain-containing protein tyrosinephosphatase
Publisher
ELSEVIER SCIENCE INC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Reactive oxygen species (ROS) produced upon collagen stimulation are implicated in propagating various platelet-activating pathways. Among ROS-producing enzymes, NADPH oxidase (NOX) is largely responsible for collagen receptor-dependent ROS production. Therefore, NOX has been proposed as a novel target for the development of antiplatelet agent. We here investigate whether resveratrol inhibits collagen-induced NOX activation and further examine the effects of resveratrol on ROS-dependent signaling pathways in collagen-stimulated platelets. Collagen-induced superoxide anion production in platelets was inhibited by resveratrol. Resveratrol suppressed collagen-induced phosphorylation of p47(Phox), a major regulatory subunit of NOX. Correlated with the inhibitory effects on NOX, resveratrol protected SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) from ROS-mediated inactivation and subsequently attenuated the specific tyrosine phosphorylation of key components (spleen tyrosine kinase, Vavl, Bruton's tyrosine kinase, and phospholipase C gamma 2) for collagen receptor signaling cascades. Resveratrol also inhibited downstream responses such as cytosolic calcium elevation, P-selectin surface exposure, and integrin-alpha Illa beta 3 activation. Furthermore, resveratrol inhibited platelet aggregation and adhesion in response to collagen. The antiplatelet effects of resveratrol through the inhibition of NOX-derived ROS production and subsequent oxidative inactivation of SHP-2 suggest that resveratrol is a potential compound for prevention and treatment of thrombovascular diseases. (C) 2015 Elsevier Inc. All rights reserved.
DOI
10.1016/j.freeradbiomed.2015.10.413
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약학대학 > 약학과 > Journal papers
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