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.
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.
Delaney
Jimmy
J
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.
Chiarello
Roselynn
R
Villar
David
D
Kandalam
Umadevi
U
Castejon
Ana Maria
AM
Clark
Michelle A
MA
D000199:Actins / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D012333:RNA, Messenger; D000804:Angiotensin II; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one