Translational Regulation of Ang Ii Type 1 Receptors in Proliferating Vascular Smooth Muscle Cells.
From: Georgetown University, 4000 Reservoir Road, NW, Washington, DC 20057, USA.
American journal of physiology. Regulatory, integrative and comparative physiology
- Publish Date: Jan 2006
- ISSN: 0363-6119
- Volume: 290
- Issue: 1
- Pages: R50-6
- Medium: Print
- Language: English
- Citation (JAMA): Lee Sunghou, Ji Hong, Wu Zheng, et al. Translational Regulation of Ang Ii Type 1 Receptors in Proliferating Vascular Smooth Muscle Cells.. Am. J. Physiol. Regul. Integr. Comp. Physiol. Jan 2006;290:R50-6
Abstract
The current study examined angiotensin receptor (ATR) regulation in proliferating rat aortic vascular smooth muscle cells (VSMCs) in culture. Radioligand competition analysis coupled with RNase protection assays (RPAs) revealed that angiotensin type 1a receptor (AT(1a)R) densities (B(max)) increased by 30% between 5 and 7 days in culture [B(max) (fmol/mg protein): day 5, 379 +/- 8.4 vs. day 7, 481 +/- 12, n = 3, P < 0.05] under conditions in which no significant changes in AT(1a)R mRNA expression occurred [in RPA arbitrary units (AU): day 5, 0.23 +/- 0.01 vs. day 7, 0.24 +/- 0.04, n = 4] or in mRNA synthesis determined by nuclear run-on assays [AU: day 5, 0.35 +/- 0.14 vs. day 7, 0.33 +/- 0.11, n = 5]. In contrast, polysome distribution analysis indicated that AT(1a)R mRNA was more efficiently translated in day 7 cells compared with day 5 [% of AT(1a)R mRNA in fraction 2 out of total AT1R mRNA recovered from the sucrose gradient: day 5, 20.9 +/- 9.9 vs. day 7, 56.8 +/- 5.6, n = 3, P < 0.001]. Accompanying the polysome shift was 50% less RNA-protein complex (RPC) formation between VSMC cytosolic RNA binding proteins in day 7 cells compared with 5-day cultures and the 5’ leader sequence (5’LS) of the AT(1a)R [5’LS RPC (AU): day 5, 0.62 +/- 0.15 vs. day 7, 0.23 +/- 0.03; n = 4, P < 0.05] and also with exon 2 [Exon 2 RPC (AU): day 5, 35.0 +/- 5.7 vs. day 7, 17.2 +/- 3.6; n = 4, P < 0.05]. Taken together, these results suggest that AT(1a)R expression is regulated by translation during VSMC proliferation in part by RNA binding proteins that interact within exon 2 in the 5’LS of the AT(1a)R mRNA.
Mesh Headings (Keywords): Animals, Aorta, Cell Proliferation, Cells, Cultured, Gene Expression Regulation, Muscle, Smooth, Vascular, Protein Binding, Protein Biosynthesis, RNA, Messenger, Rats, Rats, Inbred F344, Receptor, Angiotensin, Type 1
Check for Full Text / PubMed Unique Identifier (PMID): 16123226
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