ERK5对体外血小板活化及在体血栓的影响
发布时间：2018-09-03 13:13
【摘要】：目的:探讨细胞外信号调节激酶5(ERK5)对体外血小板聚集及在体血栓的影响及机制。方法:采用Western blot对人血小板中ERK5的表达及其在血小板活化后的磷酸化水平进行检测;采用血小板聚集仪检测ERK5特异性抑制剂XMD8-92对血小板聚集及致密颗粒释放的影响;采用Fe Cl3颈动脉血栓模型检测ERK5对在体血栓的影响;采用Western blot检测XMD8-92对蛋白激酶B(Akt)和人第10号染色体缺失的磷酸酶及张力蛋白同源蛋白(PTEN)磷酸化的影响。结果:人血小板中存在ERK5的稳定表达,其磷酸化水平在血小板活化后显著升高(P0.05)。XMD8-92可抑制多种血小板激活剂引起的血小板聚集和致密颗粒释放(P0.05)。Western blot结果表明,XMD8-92可通过下调PTEN Ser370位点磷酸化而增强PTEN的活性,从而抑制Akt的磷酸化,这种抑制效果也通过血小板特异PTEN基因敲除小鼠得到了验证。在体血栓研究表明,XMD8-92经尾静脉给药,可显著延长小鼠第一次颈动脉血栓的形成时间。结论:ERK5可通过影响PTEN的磷酸化调节Akt的活化,进而影响到体外血小板的聚集和在体血栓的形成。
[Abstract]:Aim: to investigate the effect and mechanism of extracellular signal-regulated kinase 5 (ERK5) on platelet aggregation and thrombosis in vitro. Methods: the expression of ERK5 in human platelets and its phosphorylation after platelet activation were detected by Western blot, and the effects of XMD8-92, a specific inhibitor of ERK5, on platelet aggregation and release of dense granules were detected by platelet aggregator. The effect of ERK5 on thrombus in vivo was detected by Fe Cl3 carotid thrombosis model, and the effect of XMD8-92 on phosphorylation of protein kinase B (Akt), phosphatase and tensin homologous protein (PTEN) in human chromosome 10 was detected by Western blot. Results: there was a stable expression of ERK5 in human platelets. The phosphorylation level of XMD8-92 increased significantly after platelet activation (P0.05). XMD8-92 inhibited platelet aggregation and dense particle release induced by many platelet activators (P0.05). Western blot results showed that XMD8-92 could enhance the activity of PTEN by down-regulating phosphorylation of PTEN Ser370 sites. Thus, the phosphorylation of Akt was inhibited, which was also demonstrated by platelet specific PTEN knockout mice. In vivo thrombus studies showed that XMD8-92 could significantly prolong the formation time of the first carotid thrombosis in mice. Conclusion the activation of Akt can be regulated by the phosphorylation of PTEN, which may affect platelet aggregation in vitro and thrombosis in vivo.
【作者单位】： 复旦大学附属华山医院心内科;
【基金】：国家自然科学基金资助项目(No.81270278) 上海市科委基金资助项目(No.16411965600)
【分类号】：R54
本文编号：2220078
[Abstract]:Aim: to investigate the effect and mechanism of extracellular signal-regulated kinase 5 (ERK5) on platelet aggregation and thrombosis in vitro. Methods: the expression of ERK5 in human platelets and its phosphorylation after platelet activation were detected by Western blot, and the effects of XMD8-92, a specific inhibitor of ERK5, on platelet aggregation and release of dense granules were detected by platelet aggregator. The effect of ERK5 on thrombus in vivo was detected by Fe Cl3 carotid thrombosis model, and the effect of XMD8-92 on phosphorylation of protein kinase B (Akt), phosphatase and tensin homologous protein (PTEN) in human chromosome 10 was detected by Western blot. Results: there was a stable expression of ERK5 in human platelets. The phosphorylation level of XMD8-92 increased significantly after platelet activation (P0.05). XMD8-92 inhibited platelet aggregation and dense particle release induced by many platelet activators (P0.05). Western blot results showed that XMD8-92 could enhance the activity of PTEN by down-regulating phosphorylation of PTEN Ser370 sites. Thus, the phosphorylation of Akt was inhibited, which was also demonstrated by platelet specific PTEN knockout mice. In vivo thrombus studies showed that XMD8-92 could significantly prolong the formation time of the first carotid thrombosis in mice. Conclusion the activation of Akt can be regulated by the phosphorylation of PTEN, which may affect platelet aggregation in vitro and thrombosis in vivo.
【作者单位】： 复旦大学附属华山医院心内科;
【基金】：国家自然科学基金资助项目(No.81270278) 上海市科委基金资助项目(No.16411965600)
【分类号】：R54
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