Calmodulin-dependent activation of p38 and p42/44 mitogen-activated protein kinases contributes to c-fos expression by calcium in PC12 cells:: modulation by nitric oxide
Calmodulin-dependent activation of p38 and p42/44 mitogen-activated protein kinases contributes to c-fos expression by calcium in PC12 cells:: modulation by nitric oxide
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DOI：
10.1016/s0169-328x(99)00280-6
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发表时间：
2000-01-10
期刊：
影响因子：
--
通讯作者：
Park, HT
中科院分区：
文献类型：
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作者：
Lee, SA;Park, JK;Park, HT
钙离子和一氧化氮（NO）是神经细胞活性依赖性即刻早期基因（IEG）表达的重要信使。在本研究中，我们研究了两个丝裂原活化蛋白（MAP）激酶，细胞外信号调节蛋白激酶（ERK）和p38 MAP激酶（p38激酶）在钙和NO诱导的PC 12细胞c-fos表达的作用。膜去极化诱导的钙增加激活ERK和p38激酶在5分钟内。ERK和p38激酶的激活钙是一个钙调蛋白依赖性的过程，因为预处理的W13或calmidazolium，特异性钙调蛋白拮抗剂，阻断钙诱导的激活MAP激酶。MER抑制剂（PD 98059）或p38激酶抑制剂（SB 203580）预处理可显著降低钙诱导的c-fos表达。这一发现表明，钙调素依赖的ERK和p38激酶的激活参与钙诱导的c-fos表达。然而，硝普钠和SIN-1，已知释放NO，剂量依赖性激活ERK。PD 98059可部分抑制NO诱导的c-fos表达。我们还观察到，NO剂量依赖性地增强不仅钙诱导的c-fos表达，但也钙诱导的ERK激活。在PD 98059的存在下，没有观察到NO对钙诱导的c-fos表达的放大。这一结果表明，钙和NO信号汇聚到MEK/ERK途径，从而增强IEG在神经元细胞中的表达。(C)2000 Elsevier Science B. V.保留所有权利。
Calcium and nitric oxide (NO) are important messengers for the activity-dependent immediate-early gene (IEG) expressions in neuronal cells. In the present study, we have investigated the roles of two mitogen-activated protein (MAP) kinases, extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase (p38 kinase) in calcium- and NO-induced c-fos expression in PC12 cells. Membrane depolarization-induced calcium increases activated both ERK and p38 kinase within 5 min. The activation of both ERK and p38 kinase by calcium was a calmodulin-dependent process since the pretreatment of W13 or calmidazolium, specific calmodulin antagonists, blocked calcium-induced activation of both MAP kinases. Calcium-induced c-fos expression was significantly reduced by the pretreatment of either MER inhibitor (PD98059) or p38 kinase inhibitor (SB203580). This finding indicates that the calmodulin-dependent activation of ERK and p38 kinase is involved in calcium-induced c-fos expression. However, sodium nitroprusside and SIN-1, known to release NO, dose-dependently activated only ERK. NO-induced c-fos expression was partially inhibited by the PD98059. We also observed that NO dose-dependently potentiates not only calcium-induced c-fos expression but also calcium-induced ERK activation. In the presence of PD98059, the amplification of calcium-induced c-fos expression by NO was not observed. This result suggests that calcium- and NO-signals converge into the MEK/ERK pathway, thereby enhance IEG expressions in neuronal cells. (C) 2000 Elsevier Science B.V. All rights reserved.