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
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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 |
推荐引用方式 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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