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Peroxiredoxin II is an antioxidant enzyme that negatively regulates collagen-stimulated platelet function

Title
Peroxiredoxin II is an antioxidant enzyme that negatively regulates collagen-stimulated platelet function
Authors
Jang J.Y.Wang S.B.Min J.H.Chae Y.H.Baek J.Y.Yu D.-Y.Chang T.-S.
Ewha Authors
창동신
SCOPUS Author ID
창동신scopus
Issue Date
2015
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 290, no. 18, pp. 11432 - 11442
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Collagen-induced platelet signaling is mediated by binding to the primary receptor glycoprotein VI (GPVI). Reactive oxygen species produced in response to collagen have been found to be responsible for the propagation of GPVI signaling pathways in platelets. Therefore, it has been suggested that antioxidant enzymes could down-regulate GPVI-stimulated platelet activation. Although the antioxidant enzyme peroxiredoxin II (PrxII) has emerged as having a role in negatively regulating signaling through various receptors by eliminating H<inf>2</inf>O<inf>2</inf> generated upon receptor stimulation, the function of PrxII in collagen-stimulated platelets is not known. We tested the hypothesis that PrxII negatively regulates collagenstimulated platelet activation. We analyzed PrxII-deficient murine platelets. PrxII deficiency enhanced GPVI-mediated platelet activation through the defective elimination of H<inf>2</inf>O<inf>2</inf> and the impaired protection of SH2 domain-containing tyrosine phosphatase 2 (SHP-2) against oxidative inactivation, which resulted in increased tyrosine phosphorylation of key components for the GPVI signaling cascade, including Syk, Btk, and phospholipase Cγ2. Interestingly, PrxII-mediated antioxidative protection of SHP-2 appeared to occur in the lipid rafts. PrxII-deficient platelets exhibited increased adhesion and aggregation upon collagen stimulation. Furthermore, in vivo experiments demonstrated that PrxII deficiency facilitated platelet-dependent thrombus formation in injured carotid arteries. This study reveals that PrxII functions as a protective antioxidant enzyme against collagenstimulated platelet activation and platelet-dependent thrombosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.
DOI
10.1074/jbc.M115.644260
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약학대학 > 약학과 > Journal papers
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