Klar, Juergen and Sigl, Martin and Obermayer, Birgit and Schweda, Frank and Kramer, Bernhard K. and Kurtz, Armin (2005) Calcium inhibits renin gene expression by transcriptional and posttranscriptional mechanisms. HYPERTENSION, 46 (6). pp. 1340-1346. ISSN 0194-911X,
Full text not available from this repository. (Request a copy)Abstract
The aim of this study was to investigate the role of cytosolic calcium for renin gene expression in juxtaglomerular cells. For this purpose, we used the immortalized juxtaglomerular mouse cell line As4.1. To increase cytosolic calcium concentration, we treated the cells with thapsigargin and cyclopiazonic acid, inhibitors of the endoplasmatic reticulum Ca- ATPase. Thapsigargin and cyclopiazonic acid inhibited renin gene expression in a characteristic time and concentration-dependent manner. This effect was concentration-dependently blocked by BAPTA-AM, an intracellular Ca2+ chelator. Pharmacological blocking of protein kinase C activity by calphostin, Go6976, and Go6983 did not change the effect of thapsigargin on renin gene expression. Experiments with renin1(C)-promoter-reporter constructs revealed that thapsigargin inhibited renin gene transcription. Analysis of deletion constructs of the renin1(C) promoter indicated that regulatory elements involved in the calcium-mediated inhibition of renin gene transcription are located in the enhancer region of the renin gene and that >= 3 transcription factor-binding sites are involved in this process. In addition, thapsigargin reduced the renin mRNA half-life from 10 hours (control conditions) to 4 hours. Knockdown studies with small interfering RNA directed to dynamin-1 mRNA revealed that dynamin-1 is likely to be involved in the calcium-mediated destabilization of renin mRNA. These data suggest that calcium inhibits renin gene expression in juxtaglomerular cells via a concerted action of inhibition of renin gene transcription and destabilization of renin mRNA.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESSENGER-RNA STABILITY; PROTEIN-KINASE-C; 3'-UNTRANSLATED REGION; JUXTAGLOMERULAR CELLS; RESPONSIVE ELEMENT; TRANSGENIC MICE; IDENTIFICATION; SECRETION; CAMP; REGULATOR; calcium; renin-angiotensin-aldosterone system; thapsigargin; mRNA stability |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Apr 2021 08:54 |
| Last Modified: | 14 Apr 2021 08:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35355 |
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