Todorov, Vladimir T. and Voelkl, Simon and Mueller, Markus and Bohla, Alexander and Klar, Jürgen and Kunz-Schughart, Leoni A. and Hehlgans, Thomas and Kurtz, Armin (2004) Tumor necrosis factor-alpha activates NF kappa B to inhibit renin transcription by targeting cAMP-responsive element. JOURNAL OF BIOLOGICAL CHEMISTRY, 279 (2). pp. 1458-1467. ISSN 0021-9258, 1083-351X
Full text not available from this repository.Abstract
Tumor necrosis factor-alpha (TNFalpha) is known to inhibit renin gene expression in juxtaglomerular cells, which are the main source of renin in vivo. In the present study we aimed to characterize the intracellular mechanisms of TNFalpha signaling to renin gene in the mouse juxtaglomerular cell line As4.1. TNFalpha was found to activate NFkappaB, which is one of the principal intracellular mediators of TNFalpha signal transduction. Constitutive activation of NFkappaB suppressed renin gene transcription, but NFkappaB appeared not to target the NFkappaB binding sites in the renin promoter. Thus, NFkappaB, but not the canonical NFkappaB binding sequences in the renin promoter, seemed to be involved in the suppression of renin transcription by TNFalpha. Deletion/mutation analysis revealed that the effect of TNFalpha on renin gene is transmitted by a cAMP-responsive element (CRE) located at -2697 to -2690. Mobility shift/supershift assays evidenced for the presence of NFkappaB proteins in the complex that binds to mouse renin CRE. Our results strongly suggest that NFkappaB mediates the effect of TNFalpha on renin transcription targeting a CRE in the mouse renin promoter.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-TRANSCRIPTION; JUXTAGLOMERULAR CELLS; TRANSGENIC MICE; LEUCINE ZIPPER; EXPRESSION; BINDING; PROTEINS; PROMOTER; RECEPTOR; FAMILY; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Pathologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Jul 2021 08:01 |
| Last Modified: | 23 Jul 2021 08:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38082 |
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