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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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Abstract

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.

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Acknowledgments

This work was supported in part by National Heart, Lung and Blood Institutes Grant HL-077199 and a President’s Faculty Research & Development Grant from Nova Southeastern University. We are grateful to Drs. E. Ann Tallant and Debra Diz for their thoughtful suggestions in the preparation of this manuscript.

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  1. 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

    Jimmy Delaney, Roselynn Chiarello, David Villar, Umadevi Kandalam, Ana Maria Castejon & Michelle A. Clark

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  1. Jimmy Delaney
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Correspondence to Michelle A. Clark.

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Delaney, J., Chiarello, R., Villar, D. et al. 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. Neurochem Res 33, 545–550 (2008). https://doi.org/10.1007/s11064-007-9474-y

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