中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Prohibitins are involved in protease-activated receptor 1-mediated platelet aggregation

文献类型:期刊论文

作者Zhang Y1; Wang Y1,2; Xiang Y1; Lee WH1; Zhang Y[*]1
刊名JOURNAL OF THROMBOSIS AND HAEMOSTASIS
出版日期2012
卷号10期号:3页码:411-418
关键词platelets prohibitin protease-activated receptor 1 thrombin
通讯作者zhangy@mail.kiz.ac.cn
合作状况其它
英文摘要Background: Prohibitins (PHBs), comprising the two homologous members PHB1 and PHB2, are ubiquitously expressed and highly conserved. The membrane PHBs have been reported to be involved in typhoid fever, obesity, and cancer metastasis. Proteomic studies have revealed the presence of PHBs in human platelets, but the roles of PHBs during platelet aggregation are unknown.Objectives: To investigate the role of PHBs in platelet aggregation. Methods and results: PHB1 and PHB2 were detected on the surfaces of human platelets by flow cytometry and confocal microscopy. The PHBs were distributed in lipid rafts, as determined by sucrose density centrifugation. In addition, the PHBs were associated with protease-activated receptor1 (PAR1), as determined by Bm-TFF2 (a PAR1 agonist)-affinity chromatography, coimmunoprecipitation, and confocal microscopy. The platelet aggregation, aIIb beta 3 activation, granular secretion and calcium mobilization stimulated by low concentrations of thrombin (0.05 U mL-1) or PAR1-activating peptide (PAR1-AP) (20 mu m) were reduced or abolished as a result of the blockade of PHBs by anti-PHB antibodies or their Fab fragments; however, the same results were not obtained with induction by high concentrations of thrombin (0.6 U mL-1) or protease-activated receptor4-activating peptide (300 mu m). The calcium mobilization in MEG-01 megakaryocytes stimulated by PAR1-AP was significantly suppressed by PHB depletion with RNA interference against PHB1 and PHB2. Conclusions: PHBs are localized on the human platelet membrane and are involved in PAR1-mediated platelet aggregation. Until recently, PHBs were unknown as regulators of PAR1 signaling, and they may be effective targets for antiplatelet therapy.
收录类别SCI
资助信息his work was supported by grants from the National Basic Research Program of China (973 Program, 2010CB529800) and the National Natural Science Foundation of China (NSFC-Yunnan joint funding U1132601, 30630014, and 30870304) to Y. Zhang.
语种英语
WOS记录号WOS:000300876600011
公开日期2012-05-10
源URL[http://159.226.149.42:8088/handle/152453/6933]  
专题昆明动物研究所_动物活性蛋白多肽组学
昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan
2.Graduate School of the Chinese Academy of Sciences, Beijing, China
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GB/T 7714
Zhang Y,Wang Y,Xiang Y,et al. Prohibitins are involved in protease-activated receptor 1-mediated platelet aggregation[J]. JOURNAL OF THROMBOSIS AND HAEMOSTASIS,2012,10(3):411-418.
APA Zhang Y,Wang Y,Xiang Y,Lee WH,&Zhang Y[*].(2012).Prohibitins are involved in protease-activated receptor 1-mediated platelet aggregation.JOURNAL OF THROMBOSIS AND HAEMOSTASIS,10(3),411-418.
MLA Zhang Y,et al."Prohibitins are involved in protease-activated receptor 1-mediated platelet aggregation".JOURNAL OF THROMBOSIS AND HAEMOSTASIS 10.3(2012):411-418.

入库方式: OAI收割

来源:昆明动物研究所

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