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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 Yong; Min, Ji Hyun; Wang, Su Bin; Chae, Yun Hee; Baek, Jin Young; Kim, Myunghee; Ryu, Jae-Sang; Chang, Tong-Shin
- Ewha Authors
- 창동신; 류재상
- SCOPUS Author ID
- 창동신; 류재상
- Issue Date
- 2015
- Journal Title
- FREE RADICAL BIOLOGY AND MEDICINE
- ISSN
- 0891-5849
1873-4596
- Citation
- FREE RADICAL BIOLOGY AND MEDICINE vol. 89, pp. 842 - 851
- Keywords
- Resveratrol; Antiplatelet; Reactive oxygen species; NADPH oxidase; SH-2 domain-containing protein tyrosine; phosphatase
- Publisher
- ELSEVIER SCIENCE INC
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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