Thromboxane A2 receptor-mediated G12/13-dependent glial morphological change
Thromboxane A2 receptor-mediated G12/13-dependent glial morphological change
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DOI：
10.1016/j.ejphar.2006.06.062
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发表时间：
2006-09-18
影响因子：
5
通讯作者：
Nakahata, Norimichi
中科院分区：
文献类型：
--
作者：
Honma, Shigeyoshi;Saika, Manami;Nakahata, Norimichi
神经胶质细胞表达血栓素A(2)受体，但其生理作用尚不清楚。本研究检测了1321N1人星形细胞瘤细胞血栓素A(2)受体介导的形态学变化。血栓素A(2)受体激动剂U46619和STA(2)使二丁基环AMP预处理后的细胞形态从星状迅速转变为纺锤形，但氨基酚和组胺都没有引起这种变化，提示G途径可能不是导致这种变化的主要途径。Rho激酶抑制剂Y-27632抑制了U46619诱导的形态变化，U46619增加了gtp结合形式的RhoA，并伴有肌动蛋白应激纤维的形成。这些反应通过抑制G（12/13）信号通路的p115-RGS的表达而减少。U46619还主要通过G(12/13)-Rho途径引起细胞外信号调节激酶（ERK）的磷酸化和[(3)H]胸苷的掺入。这些结果表明，血栓素A受体的刺激主要通过激活G12/13引起胶质细胞的形态改变和增殖。(c) 2006 Elsevier B.V.版权所有
Glial cells express thromboxane A(2) receptor, but its physiological role remains unknown. The present study was performed to examine thromboxane A(2) receptor-mediated morphological change in 1321N1 human astrocytoma cells. Thromboxane A(2) receptor agonists U46619 and STA(2) caused a rapid morphological change to spindle shape from stellate form of the cells pretreated with dibutyryl cyclic AMP, but neither carbachol nor histamine caused the change, suggesting that G, pathway may not mainly contribute to the change. Rho kinase inhibitor Y-27632 inhibited U46619-induced morphological change, and U46619 increased the GTP-bound form of RhoA accompanied with actin stress fiber formation. These responses were reduced by expression of p115-RGS that inhibits G(12/13) signaling pathway. U46619 also caused the phosphorylation of extracellular signal-regulated kinase (ERK) and [(3)H]thymidine incorporation mainly through G(12/13)-Rho pathway. These results suggest that stimulation of thromboxane A, receptor causes the morphological change with proliferation mainly through G12/13 activation in glial cells. (c) 2006 Elsevier B.V. All rights reserved.