期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 89, 期 -, 页码 842-851出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2015.10.413
关键词
Resveratrol; Antiplatelet; Reactive oxygen species; NADPH oxidase; SH-2 domain-containing protein tyrosine; phosphatase
资金
- Bio & Medical Technology Development Program of the NRF grant - Korean Ministry of Science, ICT and future Planning (MSIP) [NRF-2015M3A9B6029133]
- Health Technology R&D Project - Korean Ministry of Health Welfare [HI13C1046]
- National Research Foundation of Korea [2015M3A9B6029133] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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