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

Cited 13 time in scopus
Metadata Downloads
Title
Peroxiredoxin II is an antioxidant enzyme that negatively regulates collagen-stimulated platelet function
Author(s)
J Y Jang; S B Wang; J H Min; Y H Chae; J Y Baek; Dae Yeul Yu; T S Chang
Bibliographic Citation
Journal of Biological Chemistry, vol. 290, no. 18, pp. 11432-11442
Publication Year
2015
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 H2O2 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 H2O2 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.
ISSN
0021-9258
Publisher
Amer Soc Biochemistry Molecular Biology Inc
DOI
http://dx.doi.org/10.1074/jbc.M115.644260
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.