RhoA and lysophosphatidic acid are involved in the actin cytoskeleton reorganization of astrocytes exposed to ethanol
RhoA and lysophosphatidic acid are involved in the actin cytoskeleton reorganization of astrocytes exposed to ethanol
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DOI：
10.1002/jnr.10594
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发表时间：
2003-05-15
影响因子：
4.2
通讯作者：
Guerri, C
中科院分区：
文献类型：
--
作者：
Guasch, RM;Tomas, M;Guerri, C
星形胶质细胞在维持成人和发育中的神经系统的神经元功能中起着重要作用。乙醇暴露在星形胶质细胞形成过程中引起深刻的改变，影响重要的细胞功能，包括细胞内蛋白质运输。由于肌动蛋白细胞骨架在细胞内蛋白运输中起着至关重要的作用，本研究的目的是分析乙醇对肌动蛋白细胞骨架组织的影响以及RhoA信号通路在这些影响中的作用。我们发现RhoA和溶血磷脂酸（LPA）， RhoA的上游激活剂，刺激原代培养皮层星形胶质细胞中应力纤维的形成和局灶黏附。将培养的星形胶质细胞暴露于不同浓度的乙醇中，使肌动蛋白细胞骨架严重破坏，导致细胞周围形成肌动蛋白环，减少局灶黏附蛋白的含量。此外，LPA处理或RhoA转染恢复了乙醇诱导的星形胶质细胞中肌动蛋白的改变，而转染无活性RhoA突变体则无法恢复肌动蛋白环的组织。此外，C3外泌酶抑制内源性RhoA可有效阻断乙醇诱导的肌动蛋白环形成。这些结果表明，酒精对肌动蛋白细胞骨架组织的影响是通过RhoA信号通路介导的。肌动蛋白组织的破坏可能损害重要的星形胶质细胞功能，参与乙醇诱导的星形胶质细胞和脑发育过程中的损伤。(C) 2003 Wiley-Liss, Inc。
Astroglial cells play an important role in maintaining neuronal function in the adult and in the developing nervous system. Ethanol exposure induces profound alterations in the astrogliogenesis process, affecting important cell functions, including intracellular protein trafficking. Because the actin cytoskeleton plays a crucial role in intracellular protein transport, the aim of the present study was to analyze the effects of ethanol on actin cytoskeleton organization and the involvement of the RhoA signaling pathway in these effects. We show that RhoA and lysophosphatidic acid (LPA), an upstream activator of RhoA, stimulate the formation of stress fibers and focal adhesion in cortical astrocytes in primary culture. Exposure of cultured astrocytes to different concentrations of ethanol profoundly disorganizes the actin cytoskeleton, leading to the formation of actin rings at the cell periphery and decreasing the content of focal adhesion proteins. Furthermore, LPA treatment or RhoA transfection revert the ethanol-induced actin alterations in astrocytes, whereas transfection with an inactive mutant of RhoA is unable to revert the actin ring organization. In addition, inhibition of endogenous RhoA by C3 exoenzyme effectively blocks ethanol-induced actin ring formation. These results suggest that the effects of alcohol on actin cytoskeleton organization are mediated by the RhoA signaling pathway. Disruptions in actin organization may impair important astrocyte functions, participating in ethanol-induced astroglial and brain damage during development. (C) 2003 Wiley-Liss, Inc.