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[人红细胞膜蛋白激酶在变形性和聚集性变化中的作用]

[Role of protein kinases of human red cell membrane in deformability and aggregation changes].

作者信息

Murav'ev A V, Maĭmistova A A, Tikhomirova I A, Bulaeva S V, Mikhaĭlov P V, Murav'ev A A

出版信息

Fiziol Cheloveka. 2012 Mar-Apr;38(2):94-100.

PMID:22679802
Abstract

The proteomic analysis has showed that red cell membrane contains several kinases and phosphatases. Therefore the aim of this study was to investigate the role of protein kinases of human red cell membrane in deformability and aggregation changes. Exposure of red blood cells (RBCs) to some chemical compounds led to change in the RBC microrheological properties. When forskolin (10 microM), an adenylyl cyclase (AC) and a protein kinase A (PKA) stimulator was added to RBC suspension, the RBC deformability (RBCD) was increased by 20% (p < 0.05). Somewhat more significant deformability rise appeared after RBC incubation with dB-AMP (by 26%; p < 0.01). Red cell aggregation (RBCA) was significantly decreased under these conditions (p < 0.01). Markedly less changes of deformability was found after RBC incubation with protein kinase stimulator C (PKC)--phorbol 12-myristate 13-acetate (PMA). This drug reduced red cell aggregation only slightly. It was inhibited red cell tyrosine phosphotase activity by N-vanadat and was obtained a significant RBCD rise and RBCA lowering. The similar effect was found when cells were incubated with cisplatin as a tyrosine protein kinase (TPK) activator. It is important to note that a selective TPK inhibitor--lavendustin eliminated the above mention effects. On the whole the total data clearly show that the red cell aggregation and deformation changes were connected with an activation of the different intracellular signaling pathways.

摘要

蛋白质组学分析表明红细胞膜含有多种激酶和磷酸酶。因此,本研究的目的是探讨人红细胞膜蛋白激酶在变形性和聚集性变化中的作用。红细胞(RBC)暴露于某些化合物会导致RBC微观流变学性质发生变化。当向RBC悬液中加入福斯可林(10微摩尔),一种腺苷酸环化酶(AC)和蛋白激酶A(PKA)刺激剂时,RBC变形性(RBCD)增加了20%(p<0.05)。RBC与dB-AMP孵育后,变形性有更显著的升高(升高26%;p<0.01)。在这些条件下,红细胞聚集(RBCA)显著降低(p<0.01)。RBC与蛋白激酶刺激剂C(PKC)——佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)孵育后,变形性变化明显较小。这种药物仅轻微降低红细胞聚集。N-钒酸盐抑制了红细胞酪氨酸磷酸酶活性,导致RBCD显著升高和RBCA降低。当细胞与作为酪氨酸蛋白激酶(TPK)激活剂的顺铂孵育时,也发现了类似的效果。需要注意的是,一种选择性TPK抑制剂——拉文达ustin消除了上述作用。总体而言,所有数据清楚地表明,红细胞聚集和变形变化与不同细胞内信号通路的激活有关。

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