ISSN:
1573-4919
Keywords:
angiotensin
;
down regulation
;
luciferase
;
retroviral gene transfer
;
nuclear repressors
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Growth factors and agonists of both Gas and Gαq-coupled receptor agonists each down regulate angiotensin AT1 receptor gene expression in vascular smooth muscle cells. To test whether the transcription factor CREB is in the pathway involved in modulation of AT1-receptor gene expression, AT1 receptor mRNA levels were measured after stimulation with forskolin, angiotensin II and PDGF-BB in VSMC expressing the inducible cAMP early repressor protein, ICERIIγ, fused to the green fluorescent protein (eGFP). This fusion protein inhibits luciferase induction from promoters driven by either CREB response elements (CRE) or, unexpectedly, by tetradecanoylphorbol acetate response elements (TRE), which bind activator protein (AP-1). EGFP-ICERIIγ expression inhibits occupancy of CRE and TRE elements by endogenous VSMC nuclear proteins. Nevertheless, agonist-induced AT1-receptor mRNA down regulation is unaffected by eGFP-ICERIIγ expression. Although CREB transcription is activated by multiple classes of agonists in VSMC, and ICER can inhibit agonist-induced transcription mediated by both CREB and AP-1 enhancers, these transcription factors are not obligate components of the pathways regulating AT1-R gene expression in rat VSMC.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007173424949
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