Role of ERK5 in platelet activation in vitro and arterial thrombosis in vivo / 中国病理生理杂志

ABSTRACT

AIM:To investigate the role of extracellular signal-regulated kinase 5(ERK5) in platelet aggrega-tion in vitro and arterial thrombosis in vivo. METHODS:The expression and phosphorylation levels of ERK5 in human platelet were detected by Western blot. The effects of ERK5 selective inhibitor XMD8-92 on platelet aggregation and dense granule secretion were detected by Chrono-Log aggregometer. The effect of ERK5 on in vivo thrombosis was analyzed using an FeCl3artery thrombosis model. The effects of XMD8-92 on protein kinase B (PKB/Akt) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) phosphorylation levels were determined by Western blot. RESULTS:ERK5 was stably expressed in human platelets and its phosphorylation level increased significantly after platelet activation (P<0.05). XMD8-92,a selective inhibitor of ERK5,inhibited platelet aggregation and dense granule secretion in response to several platelet stimulators (P<0.05). The results of Western blot showed that XMD8-92 inhibited Akt phosphorylation level by down-regulating PTEN Ser370 phosphorylation and enhancing PTEN activity. The pathway was further confirmed u-sing platelet specific PTEN deficiency mice. The first occlusion time was obviously extended in the mice intravenously given XMD8-92 in the FeCl3-induced carotid artery injury model. CONCLUSION:ERK5 plays a role in platelet activation and arterial thrombosis by influencing PTEN and Akt phosphorylation.