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Molecular Pharmacology

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Abstract

Enhanced angiotensin receptor type 1 mRNA degradation and induction of polyribosomal mRNA binding proteins by angiotensin II in vascular smooth muscle cells.

G Nickenig and T J Murphy
Molecular Pharmacology October 1996, 50 (4) 743-751;
G Nickenig
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Abstract

Stimulation of cultured rat thoracic aorta vascular smooth muscle cells (VSMCs) with 100 nM angiotensin II (Ang II) reduces angiotensin receptor type 1 (AT1-R) gene expression. mRNA levels are reduced to approximately 30% of control levels 4 hr after the addition of Ang II to the culture medium. The loss of mRNA remains sustained for up to 24 hr after the addition of Ang II. The half-life of the AT1-R mRNA is approximately 2 hr in cells treated with a single dose of 100 nM Ang II. This represents a 3-fold reduction from its half-life of 6 hr in nonstimulated cells, as assessed by treatment with 5,6-dichlorobenzimidazole or actinomycin D to block transcription. Thus, the AT1-R mRNA is moderately unstable in VSMC and destabilized further by treatment with Ang II. Ang II-induced AT1-R mRNA destabilization is prevented by pretreatment with transcriptional inhibitors or the protein synthesis inhibitor cycloheximide, suggesting that Ang II-induced AT1-R mRNA destabilization requires the induction of an unknown factor or factors that are postulated to mediate this effect. AT1-R mRNA levels decrease more rapidly in vitro from a polyribosomal fraction isolated from VSMC exposed for 2 hr to 100 nM Ang II compared with that from vehicle-treated cells, suggesting that polyribosomal-associated AT1-R mRNA is at least one site of action for the mRNA destabilization effect of Ang II. Ang II stimulation induces a complex of polyribosomal proteins that bind specifically in the distal 350 bases of the AT1-R mRNA. Regulation of mRNA stability accounts in part for modulation of AT1-R gene expression by Ang II in VSMCs, and Ang II-induced AT1-R mRNA polyribosomal binding proteins are associated with this phenomenon.

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Molecular Pharmacology
Vol. 50, Issue 4
1 Oct 1996
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Abstract

Enhanced angiotensin receptor type 1 mRNA degradation and induction of polyribosomal mRNA binding proteins by angiotensin II in vascular smooth muscle cells.

G Nickenig and T J Murphy
Molecular Pharmacology October 1, 1996, 50 (4) 743-751;

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Abstract

Enhanced angiotensin receptor type 1 mRNA degradation and induction of polyribosomal mRNA binding proteins by angiotensin II in vascular smooth muscle cells.

G Nickenig and T J Murphy
Molecular Pharmacology October 1, 1996, 50 (4) 743-751;
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