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首页> 外文期刊>Haematologica >Hemoglobin interaction with GP1bα induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis
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Hemoglobin interaction with GP1bα induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis

机译:血红蛋白与GP1bα的相互作用诱导血小板活化和凋亡:与血管内溶血有关的新机制

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摘要

Intravascular hemolysis increases the risk of hypercoagulation and thrombosis in hemolytic disorders. Our study shows a novel mechanism by which extracellular hemoglobin directly affects platelet activation. The binding of Hb to glycoprotein1bα activates platelets. Lower concentrations of Hb (0.37–3 μM) significantly increase the phosphorylation of signaling adapter proteins, such as Lyn, PI3K, AKT, and ERK, and promote platelet aggregation in vitro . Higher concentrations of Hb (3–6 μM) activate the pro-apoptotic proteins Bak, Bax, cytochrome c, caspase-9 and caspase-3, and increase platelet clot formation. Increased plasma Hb activates platelets and promotes their apoptosis, and plays a crucial role in the pathogenesis of aggregation and development of the procoagulant state in hemolytic disorders. Furthermore, we show that in patients with paroxysmal nocturnal hemoglobinuria, a chronic hemolytic disease characterized by recurrent events of intravascular thrombosis and thromboembolism, it is the elevated plasma Hb or platelet surface bound Hb that positively correlates with platelet activation.
机译:血管内溶血会增加溶血性疾病中高凝和血栓形成的风险。我们的研究显示了一种新的机制,通过该机制,细胞外血红蛋白直接影响血小板活化。 Hb与糖蛋白1bα的结合可激活血小板。较低的Hb浓度(0.37–3μM)会显着增加信号转导接头蛋白(如Lyn,PI3K,AKT和ERK)的磷酸化,并促进体外血小板聚集。较高浓度的Hb(3–6μM)激活促凋亡蛋白Bak,Bax,细胞色素c,caspase-9和caspase-3,并增加血小板凝块形成。血浆Hb的增加会激活血小板并促进其凋亡,并在溶血性疾病的凝集和促凝状态发展中起关键作用。此外,我们发现在阵发性夜间血红蛋白尿症(一种以血管内血栓形成和血栓栓塞复发事件为特征的慢性溶血性疾病)中,血浆血红蛋白或血小板表面结合血红蛋白升高与血小板活化呈正相关。

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