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调节红细胞聚集的信号通路。

Signaling pathways regulating red blood cell aggregation.

作者信息

Muravyov Alexei, Tikhomirova Irina

机构信息

Department of Medicine and Biology, State Pedagogical University, Yaroslavl, Russia.

出版信息

Biorheology. 2014;51(2-3):135-45. doi: 10.3233/BIR-140664.

DOI:10.3233/BIR-140664
PMID:24934258
Abstract

The exposure of red blood cells (RBC) to some hormones (epinephrine, insulin and glucagon) and agonists of α- and β-adrenergic receptors (phenylephrine, clonidine and isoproterenol) may modify RBC aggregation (RBCA). Prostaglandin E1 (PGE1) significantly decreased RBCA, and PGE2 had a similar but lesser effect. Adenylyl cyclase (AC) stimulator forskolin added to RBC suspension, caused a decrease of RBCA. More marked lowering of RBCA occurred after RBC treatment by dB-cAMP. Phosphodiesterase (PDE) inhibitors markedly reduced RBCA. Ca2+ influx stimulated by A23187 was accompanied by an increase of RBCA. The blocking of Ca2+ entry into the RBC by verapamil or the chelation of Ca2+ by EGTA led to a significant RBCA decrease. Lesser changes of aggregation were found after RBC incubation with protein kinase C stimulator phorbol 12-myristate 13-acetate (PMA). A significant inhibitory effect of tyrosine protein kinase (TPK) activator cisplatin on RBCA was revealed, while selective TPK inhibitor, lavendustin, eliminated the above mentioned effect. Taken together, the data demonstrate that changes in RBCA are connected with activation of different intracellular signaling pathways. We suggest that alterations in RBCA are mainly associated with the crosstalk between the adenylyl cyclase-cAMP system and Ca2+ control mechanisms.

摘要

红细胞(RBC)暴露于某些激素(肾上腺素、胰岛素和胰高血糖素)以及α-和β-肾上腺素能受体激动剂(去氧肾上腺素、可乐定和异丙肾上腺素)可能会改变红细胞聚集(RBCA)。前列腺素E1(PGE1)显著降低RBCA,前列腺素E2(PGE2)有类似但较弱的作用。向红细胞悬液中添加腺苷酸环化酶(AC)刺激剂福司可林会导致RBCA降低。用二丁酰环磷腺苷(dB-cAMP)处理红细胞后,RBCA降低更为明显。磷酸二酯酶(PDE)抑制剂显著降低RBCA。A23187刺激的Ca2+内流伴随着RBCA增加。维拉帕米阻断Ca2+进入红细胞或乙二醇双(2-氨基乙基醚)四乙酸(EGTA)螯合Ca2+导致RBCA显著降低。红细胞与蛋白激酶C刺激剂佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)孵育后,聚集变化较小。酪氨酸蛋白激酶(TPK)激活剂顺铂对RBCA有显著抑制作用,而选择性TPK抑制剂拉文达ustin消除了上述作用。综上所述,数据表明RBCA的变化与不同细胞内信号通路的激活有关。我们认为RBCA的改变主要与腺苷酸环化酶-cAMP系统和Ca2+调控机制之间相互作用有关。

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