title: Peroxiredoxin II is an antioxidant enzyme that negatively regulates collagen-stimulated platelet function.
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 collagen-stimulated 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 collagen-stimulated platelet activation and platelet-dependent thrombosis.
authors: From the Graduate School of Pharmaceutical Sciences and.
authors: Ji Yong
authors: JY
authors: Jang
authors: From the Graduate School of Pharmaceutical Sciences and.
authors: Su Bin
authors: SB
authors: Wang
authors: From the Graduate School of Pharmaceutical Sciences and.
authors: Ji Hyun
authors: JH
authors: Min
authors: From the Graduate School of Pharmaceutical Sciences and.
authors: Yun Hee
authors: YH
authors: Chae
authors: From the Graduate School of Pharmaceutical Sciences and.
authors: Jin Young
authors: JY
authors: Baek
authors: the Disease Model Research Laboratory, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 605-806, Korea.
authors: Dae-Yeul
authors: DY
authors: Yu
authors: From the Graduate School of Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750 and changts@ewha.ac.kr.
authors: Tong-Shin
authors: TS
authors: Chang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000503:physiopathology; D003094:Collagen / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D054464:Peroxiredoxins / Q000172:deficiency / Q000378:metabolism*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013927:Thrombosis / Q000378:metabolism / Q000503:physiopathology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D017382:Reactive Oxygen Species; C098341:platelet membrane glycoprotein VI; D014443:Tyrosine; D003094:Collagen; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: Collagen; Hydrogen Peroxide; Peroxiredoxin; Platelet; Protein-tyrosine Phosphatase (Tyrosine Phosphatase)