Ethanol inhibition of angiotensin II-stimulated Tyr705 and Ser727 STAT3 phosphorylation in cultured rat hepatocytes: relevance to activation of p42/44 mitogen-activated protein kinase.
Ethanol inhibition of angiotensin II-stimulated Tyr705 and Ser727 STAT3 phosphorylation in cultured rat hepatocytes: relevance to activation of p42/44 mitogen-activated protein kinase.
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乙醇抑制培养大鼠肝细胞中血管紧张素 II 刺激的 Tyr705 和 Ser727 STAT3 磷酸化：与 p42/44 丝裂原激活蛋白激酶的激活相关。
DOI：
10.1016/j.alcohol.2008.02.004
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Shukla,ShivendraD
中科院分区：
文献类型：
--
作者：
Weng,Yu-I;Aroor,AnnayyaR;Shukla,ShivendraD
Angiotensin (Ang) II-stimulated phosphorylation of signal transducer and activator transcription (STAT) 3 in rat hepatocytes and the effects of ethanol on this activation were investigated. Angiotensin II (100 nM) stimulated Tyr705and Ser727phosphorylation of STAT3 and formation of sis-inducing factor complexes. In the presence of U-0126 (10μM), a p42/44 mitogen-activated protein kinase (MAPK) kinase inhibitor, Ang II further increased Tyr705phosphorylation of STAT3 but completely abrogated Ser727phosphorylation of STAT3. Inhibition of p42/44MAPK also increased STAT3 DNA-binding activity. Pretreatment with ethanol (100mM) for 24h resulted in decrease in Tyr705phosphorylation of STAT3 by ethanol alone and inhibition of Tyr705 phosphorylation of STAT3 stimulated by Ang II. Although ethanol potentiates Ang II stimulated p42/44 MAPK activation in hepatocytes, ethanol inhibited Ser727phosphorylation of STAT3 stimulated by Ang II. Angiotensin II-stimulated STAT3-binding activity was not significantly affected by ethanol treatment. These results suggest a negative regulation of Ang II-stimulated STAT3 tyrosine phosphorylation and STAT3-binding activity through p42/44 MAPK activation in hepatocytes. However, ethanol modulation of Ang II-stimulated STAT3 phosphorylation occurs by MAPK independent mechanisms. Ethanol potentiation of MAPK signaling without suppression of STAT3 function may modulate the course of alcoholic liver injury.
