Monocrotaline pyrrole interacts with actin and increases thrombin-mediated permeability in pulmonary artery endothelial cells.
Monocrotaline pyrrole interacts with actin and increases thrombin-mediated permeability in pulmonary artery endothelial cells.
复制标题
野百合碱吡咯与肌动蛋白相互作用，增加肺动脉内皮细胞中凝血酶介导的通透性。
DOI：
10.1006/taap.1998.8488
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Segall,HJ
中科院分区：
文献类型：
--
作者：
Wilson,DW;Lame,MW;Dunston,SK;Taylor,DW;Segall,HJ
大鼠肺动脉高压野百合碱 (MCT) 模型中最早明显的形态变化之一是微血管渗漏。这是否代表 MCT 代谢物的直接影响，还是继发于炎症和血栓变化，仍不确定。为了确定 MCT 是否直接影响内皮细胞通透性屏障功能，我们表征了 MCT 的反应性吡咯中间体 (MCTP) 与内皮细胞肌动蛋白的相互作用，并表征了其对凝血酶介导的信号转导和单层通透性的影响。荧光显微镜观察发现，用 MCTP 处理的牛肺内皮细胞 (BPAEC) 改变了丝状肌动蛋白的分布。从用14 C-MCTP处理的BPAEC分离的肌动蛋白的相关蛋白质印迹和放射自显影显示肌动蛋白和MCTP衍生的14 C的共迁移。 MCTP 治疗不会改变细胞游离 Ca2+ 浓度，也不会干扰凝血酶介导的细胞内 Ca2+ 信号。 MCTP预处理显着增加了BPAEC单层中凝血酶介导的埃文蓝白蛋白的渗出，显然是通过增加细胞间间隙的大小来实现的。我们得出结论，MCTP 直接与肌动蛋白相互作用以改变其聚合状态，但不会显着影响内皮细胞对收缩刺激的反应。我们的结果表明，MCTP 可能通过改变细胞内连接来影响内皮细胞屏障功能。
One of the earliest morphologic changes evident in the monocrotaline (MCT) model of pulmonary hypertension in rats is microvascular leak. Whether this represents a direct effect of MCT metabolites or is secondary to inflammatory and thrombotic changes remains uncertain. To determine whether MCT directly affects endothelial cell permeability barrier function, we characterized the interaction of the reactive pyrrole intermediate of MCT (MCTP) with endothelial cell actin and characterized its effects on thrombin-mediated signal transduction and monolayer permeability. Bovine pulmonary endothelial cells (BPAEC) treated with MCTP had altered distribution of filamentous actin evident by fluorescence microscopy. Correlative Western blots and autoradiography of actin isolated from BPAEC treated with14C-MCTP showed comigration of actin and MCTP-derived14C. MCTP treatment did not alter cellular free Ca2+concentrations nor did it interfere with thrombin-mediated intracellular Ca2+signal. Pretreatment with MCTP significantly augmented the thrombin-mediated transudation of Evan's blue albumin in BPAEC monolayers apparently by increasing the size of intercellular gaps. We conclude that MCTP directly interacts with actin to alter its polymerization state but does not significantly affect endothelial cell response to contractile stimulus. Our results suggest that MCTP may affect endothelial cell barrier function through alterations in intracellular junctions.