Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
Biochem Biophys Res Commun. 2020 Jun 18;527(1):104-109. doi: 10.1016/j.bbrc.2020.04.065. Epub 2020 Apr 28.
Platelets play central role in thrombosis and haemostasis. Platelets store adenine nucleotides in their dense granules, which are released upon agonist-stimulation. Level of these nucleotides in extracellular fluid is regulated by activities of ectonucleotidases such as ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5'-nucleotidase (CD73) expressed on platelet surface. Here we demonstrate that, expression of surface-bound ectonucleotidases rose significantly in platelets, concomitant with upregulation of their enzymatic activities, when cells were stimulated with thrombin. Interestingly, inhibition of CD73 in thrombin-treated platelets led to enhanced tyrosine phosphorylation of proteins and rise in intracellular free calcium, [Ca], thus signifying the inhibitory role of the ectonucleotidase on agonist-mediated platelet signaling.
血小板在血栓形成和止血中起着核心作用。血小板在其致密颗粒中储存腺嘌呤核苷酸，这些核苷酸在激动剂刺激下释放。细胞外液中这些核苷酸的水平受血小板表面表达的胞外核苷酸酶（如外核苷酸三磷酸二磷酸水解酶-1（CD39）和外切 5'-核苷酸酶（CD73））的活性调节。在这里，我们证明当细胞用凝血酶刺激时，表面结合的胞外核苷酸酶的表达水平显著升高，同时其酶活性也上调。有趣的是，在凝血酶处理的血小板中抑制 CD73 会导致蛋白质酪氨酸磷酸化增加和细胞内游离钙 [Ca] 升高，这表明该胞外核苷酸酶对激动剂介导的血小板信号转导具有抑制作用。
