Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion
Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion
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DOI：
10.1152/ajplung.1999.277.2.l282
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发表时间：
1999-08-01
影响因子：
4.9
通讯作者：
Fanburg, BL
中科院分区：
文献类型：
--
作者：
Lee, SL;Wang, WW;Fanburg, BL
我们以前的研究表明，通过主动转运过程，5-羟色胺（5-HT）迅速升高O-2（-）。形成，刺激蛋白磷酸化，并增强牛肺动脉平滑肌细胞（SMC）的增殖。我们目前表明，1 μ M的5-HT也迅速提高磷酸化和激活的丝裂原活化蛋白（MAP）激酶细胞外信号调节激酶（ERK）1和ERK 2的SMC，和增强的磷酸化被阻断的抗氧化剂Tiron，N-乙酰-L-半胱氨酸（NAC），银杏叶提取物。用PD-98059抑制MAP激酶不能阻断增强的O-2（-.）5-HT形成。中国仓鼠肺成纤维细胞（CCL-39细胞）显示出5-HT转运蛋白和受体活性，对5-HT显示出类似的反应（即，增强有丝分裂，O-2（-.）形成以及ERK 1和ERK 2磷酸化和激活）。与SMC不同，它们也对5-HT受体激动剂有反应。我们的结论是，MAP激酶的下游信号是一个广义的细胞反应，5-HT发生继发于O-2（-。）形成，并且可以由5-HT转运蛋白或受体启动，这取决于细胞类型。
Our previous studies have shown that, through an active transport process, serotonin (5-HT) rapidly elevates O-2(-.) formation, stimulates protein phosphorylation, and enhances proliferation of bovine pulmonary artery smooth muscle cells (SMCs). We presently show that 1 mu M 5-HT also rapidly elevates phosphorylation and activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) 1 and ERK2 of SMCs, and the enhanced phosphorylation is blocked by the antioxidants Tiron, N-acetyl-L-cysteine (NAC), and Ginkgo biloba extract. inhibition of MAP kinase with PD-98059 failed to block enhanced O-2(-.) formation by 5-HT. Chinese hamster lung fibroblasts (CCL-39 cells), which demonstrate both 5-HT transporter and receptor activity, showed a similar response to 5-HT (i.e., enhanced mitogenesis, O-2(-.) formation, and ERK1 and ERK2 phosphorylation and activation). Unlike SMCs,they also responded to 5-HT receptor agonists. We conclude that downstream signaling of MAP kinase is a generalized cellular response to 5-HT that occurs secondary to O-2(-.) formation and may be initiated by either the 5-HT transporter or receptor depending on the cell type.