| Prohibitins are involved in protease-activated receptor 1-mediated platelet aggregation | |
| Zhang Yong1; Wang Y1,2; Xiang Y1; Lee WH1; Zhang Y*1; zhangy@mail.kiz.ac.cn | |
| 2012 | |
| 发表期刊 | JOURNAL OF THROMBOSIS AND HAEMOSTASIS
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| 卷号 | 10期号:3页码:411-418 |
| 合作性质 | 其它 |
| 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. |
| 关键词 | Platelets Prohibitin Protease-activated Receptor 1 Thrombin |
| 资助者 | 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. ; 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. ; 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. ; 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. |
| 收录类别 | SCI |
| 语种 | 英语 |
| 资助者 | 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. ; 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. ; 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. ; 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. |
| WOS记录号 | WOS:000300876600011 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/6933 |
| 专题 | 科研部门_生物毒素与人类疾病（张云） 科研部门_动物模型与人类重大疾病机理重点实验室 |
| 通讯作者 | zhangy@mail.kiz.ac.cn |
| 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 Yong,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 Yong,Wang Y,Xiang Y,Lee WH,Zhang Y*,&zhangy@mail.kiz.ac.cn.(2012).Prohibitins are involved in protease-activated receptor 1-mediated platelet aggregation.JOURNAL OF THROMBOSIS AND HAEMOSTASIS,10(3),411-418. |
| MLA | Zhang Yong,et al."Prohibitins are involved in protease-activated receptor 1-mediated platelet aggregation".JOURNAL OF THROMBOSIS AND HAEMOSTASIS 10.3(2012):411-418. |
| 条目包含的文件 | ||||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
| 2012051001.pdf（382KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | 请求全文 | |
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