Regulation of c-fos, c-jun and c-myc gene expression by angiotensin II in primary cultured rat astrocytes: Role of ERK1/2 MAP kinases

Regulation of c-fos, c-jun and c-myc gene expression by angiotensin II in primary cultured rat astrocytes: Role of ERK1/2 MAP kinases
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DOI:
10.1007/s11064-007-9474-y
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发表时间:
2008-03-01
影响因子:
4.4
通讯作者:
Clark, Michelle A.
Clark, Michelle A.
中科院分区:
医学3区
文献类型:
--
作者:
Delaney, Jimmy;Chiarello, Roselynn;Clark, Michelle A.

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我们以前已经表明,血管紧张素II(Ang II)刺激星形胶质细胞的生长,通过激活ERK 1/2丝裂原活化蛋白(MAP)激酶。在目前的研究中,我们确定是否血管紧张素II刺激c-fos,c-jun和c-myc在脑干星形胶质细胞培养的表达。逆转录-PCR分析显示c-fos、c-jun和c-myc mRNA被Ang II诱导。Ang II刺激c-fos、c-jun和c-myc的EC 50值分别为1.3、1.68和1.4 nM。Ang II(100 nM)诱导所有基因的峰值刺激45分钟,然后逐渐下降。PD 98059抑制ERK 1/2可减弱Ang II诱导的c-fos和c-myc mRNA表达(分别降低75%和100%),但不能阻止Ang II诱导的c-jun. These研究首次表明,在脑干星形胶质细胞中,Ang II诱导c-fos、c-myc和c-jun的表达,并表明ERK 1/2介导Ang II对c-fos和c-myc的刺激。这些数据暗示ERK 1/2 MAP激酶途径作为控制中枢神经系统中的立即早期反应基因的Ang II刺激的分歧点。
We have previously shown that angiotensin II (Ang II) stimulates astrocyte growth through activation of ERK1/2 mitogen activated protein (MAP) kinases. In the current study, we determined whether Ang II stimulates the expression of c-fos, c-jun and c-myc in brainstem astrocyte cultures. Reverse transcriptase-PCR analysis showed c-fos, c-jun, and c-myc mRNAs were induced by Ang II. The EC50 values for Ang II stimulation of c-fos, c-jun and c-myc were 1.3, 1.68 and 1.4 nM, respectively. Ang II (100 nM) induced peak stimulation for all genes by 45 min followed by a gradual decline. Inhibition of ERK1/2 by PD98059 attenuated Ang II-induced c-fos and c-myc mRNA expression (by 75% and 100%, respectively) but was ineffective in preventing Ang II induction of c-jun. These studies show for the first time in brainstem astrocytes that Ang II induces the expression of c-fos, c-myc and c-jun, and showed that ERK1/2 mediate Ang II stimulation of c-fos and c-myc. These data implicate the ERK1/2 MAP kinase pathway as a divergent point in controlling Ang II stimulation of immediate early response genes in the central nervous system.