Thrombin increases hyposmotic taurine efflux and accelerates $$ { ext{ICI}}^{ - }_{{{ ext{swell}}}} $$ and RVD in 3T3 fibroblasts by a src-dependent EGFR transactivation

Thrombin increases hyposmotic taurine efflux and accelerates $$ { ext{ICI}}^{ - }_{{{ ext{swell}}}} $$ and RVD in 3T3 fibroblasts by a src-dependent EGFR transactivation
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凝血酶通过 src 依赖性 EGFR 反式激活,增加低渗牛磺酸流出并加速 3T3 成纤维细胞中的 $$ { ext{ICI}}^{ - }_{{{ ext{swell}}}} $$ 和 RVD

DOI:
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发表时间:
2008
期刊:
Pflügers Archiv: European Journal of Physiology
影响因子:
--
通讯作者:
H. Pasantes‐morales
H. Pasantes‐morales
中科院分区:
--
文献类型:
--
作者:
E. Vázquez‐Juárez;G. Ramos;R. Lezama;S. Cruz;L. Islas;H. Pasantes‐morales

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The present study in Swiss3T3 fibroblasts examines the effect of thrombin on hyposmolarity-induced osmolyte fluxes and RVD, and the contribution of the src/EGFR pathway. Thrombin (5 U/ml) added to a 30% hyposmotic medium markedly increased hyposmotic 3H-taurine efflux (285%), accelerated the volume-sensitive Cl− current ($$ { ext{ICI}}^{ - }_{{{ ext{swell}}}} $$) and increased RVD rate. These effects were reduced (50–65%) by preventing the thrombin-induced intracellular Ca2+ [Ca2+]i rise with EGTA-AM, or with the phospholipase C (PLC) blocker U73122. Ca2+calmodulin (CaM) and calmodulin kinase II (CaMKII) also participate in this Ca2+-dependent pathway. Thrombin plus hyposmolarity increased src and EGFR phosphorylation, whose blockade by PP2 and AG1478, decreased by 30–50%, respectively, the thrombin effects on hyposmotic taurine efflux, $$ { ext{ICI}}^{ - }_{{{ ext{swell}}}} $$ and RVD. Ca2+- and src/EGFR-mediated pathways operate independently as shown by (1) the persistence of src and EGFR activation when [Ca2+]i rise is prevented and (2) the additive effect on taurine efflux, $$ { ext{ICI}}^{ - }_{{{ ext{swell}}}} $$ or RVD by simultaneous inhibition of the two pathways, which essentially suppressed these events. PLC–Ca2+- and src/EGFR-signaling pathways operate in the hyposmotic condition and because thrombin per se failed to increase taurine efflux and $$ { ext{ICI}}^{ - }_{{{ ext{swell}}}} $$ under isosmotic condition it seems that it is merely amplifying these previously activated mechanisms. The study shows that thrombin potentiates hyposmolarity-induced osmolyte fluxes and RVD by increasing src/EGFR-dependent signaling, in addition to the Ca2+-dependent pathway.
ATP 通过多种 Ca2 敏感机制调节培养的大鼠星形胶质细胞中阴离子通道介导的有机渗透剂的释放。
DOI: 10.1152/ajpcell.00330.2004
发表时间: 2005
期刊: American journal of physiology. Cell physiology
影响因子: --
作者:
Mongin,AlexanderA;Kimelberg,HaroldK
通讯作者: Kimelberg,HaroldK