Delaney Jimmy, Chiarello Roselynn, Villar David, Kandalam Umadevi, Castejon Ana Maria, Clark Michelle A
College of Pharmacy, Department of Pharmaceutical and Administrative Sciences, Cardiovascular and Metabolic Research Unit, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
Neurochem Res. 2008 Mar;33(3):545-50. doi: 10.1007/s11064-007-9474-y. Epub 2007 Sep 1.
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.
我们之前已经表明，血管紧张素II（Ang II）通过激活ERK1/2丝裂原活化蛋白（MAP）激酶来刺激星形胶质细胞生长。在当前研究中，我们确定了Ang II是否能刺激脑干星形胶质细胞培养物中c-fos、c-jun和c-myc的表达。逆转录酶-PCR分析显示，Ang II可诱导c-fos、c-jun和c-myc的mRNA表达。Ang II刺激c-fos、c-jun和c-myc的EC50值分别为1.3、1.68和1.4 nM。Ang II（100 nM）在45分钟时诱导所有基因达到峰值刺激，随后逐渐下降。用PD98059抑制ERK1/2可减弱Ang II诱导的c-fos和c-myc mRNA表达（分别降低75%和100%），但对阻止Ang II诱导c-jun无效。这些研究首次在脑干星形胶质细胞中表明，Ang II可诱导c-fos、c-myc和c-jun的表达，并表明ERK1/2介导Ang II对c-fos和c-myc的刺激。这些数据表明ERK1/2 MAP激酶途径是控制中枢神经系统中Ang II对即刻早期反应基因刺激的一个分歧点。
