Differential activation of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinases confers cadmium-induced HSP70 expression in 9L rat brain tumor cells
Differential activation of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinases confers cadmium-induced HSP70 expression in 9L rat brain tumor cells
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DOI：
10.1074/jbc.273.48.31924
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发表时间：
1998-11-27
影响因子：
4.8
通讯作者：
Chang, MDT
中科院分区：
文献类型：
--
作者：
Hung, JJ;Cheng, TJ;Chang, MDT
本文报道了用40-100 μ M的CdCl_2处理9 L大鼠脑肿瘤细胞诱导热休克蛋白（HSP）的产生，在此过程中主要涉及热休克因子（HSF）的激活。通过开发蛋白激酶抑制剂，我们进一步分析了特定蛋白激酶在上述过程中的可能参与。发现在用高浓度镉（即100 μ M）处理的细胞中，HSP 70的诱导之前是p38促分裂原活化蛋白激酶（p38（MAPK））的磷酸化和活化，而在用低浓度（60 μ M）处理的细胞中，伴随着细胞外调节蛋白激酶1和2（ERK 1/2）的磷酸化和活化。在100 μ M镉处理的细胞中，在p38（MAPK）的特异性抑制剂SB 203580存在下，HSP 70诱导和HSF 1活化都被消除。相比之下，在60 μ M镉处理的细胞中，该过程不受SB 203580的影响，但显著抑制PD 98059，它通过作用于MAPK-ERK激酶间接抑制ERK 1/2。总之，我们证明，p38（MAPK）和ERK 1/2可以同时或独立激活不同浓度的镉和信号通路参与诱导HSP 70的诱导作用于诱导磷酸化的HSF 1。因此，我们提供了第一个证据表明，p38（MAPK）和ERK信号通路可以差异参与激活的HSF 1，导致诱导HSP 70镉。
We have reported that treatment with CdCl2 at 40-100 mu M induces the heat shock proteins (HSPs) in 9L rat brain tumor cells, during which the activation of heat shock factor (HSF) is essentially involved. By exploiting protein kinase inhibitors, we further analyzed the possible participation of specific protein kinases in the above processes. It was found that induction of HSP70 in cells treated with a high concentration of cadmium (i.e. 100 mu M) is preceded by the phosphorylation and activation of p38 mitogen-activated protein kinase (p38(MAPK)), while that in cells treated with a low concentration (60 mu M) is accompanied by the phosphorylation and activation of extracellular-regulated protein kinases 1 and 2 (ERK1/2). In 100 mu M cadmium-treated cells, both HSP70 induction and HSF1 activation are eliminated in the presence of SB203580, a specific inhibitor of p38(MAPK). By contrast, in 60 mu M cadmium-treated cells, the processes are not affected by SB203580 but are significantly suppressed by PD98059, which indirectly inhibits ERK1/2 by acting on MAPK-ERK kinase. Taken together, we demonstrate that p38(MAPK) and ERK1/2 can be simultaneously or independently activated under different concentrations of cadmium and that the signaling pathways participate in the induction of HSP70 by acting on the inducible phosphorylation of HSF1. We thus provide the first evidence that both p38(MAPK) and ERK signaling pathways can differentially participate in the activation of HSF1, which leads to the induction of HSP70 by cadmium.