Angiotensin II inhibits renin gene transcription via the protein kinase C pathway

Mueller, Markus W. and Todorov, Vladimir and Kraemer, Bernhard K. and Kurtz, Armin (2002) Angiotensin II inhibits renin gene transcription via the protein kinase C pathway. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 444 (4). pp. 499-505. ISSN 0031-6768

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Abstract

Angiotensin II (ANGII) inhibits renin gene expression in vivo, a mechanism considered to be a physiologically important negative feedback of the renin-angiotensin-system. How this particular effect of ANGII is achieved at the cellular level is unknown. Our study therefore aimed to determine whether ANGII exerts a direct effect on renin gene expression and, if so, to characterise the molecular mechanisms involved. In the mouse renal juxtaglomerular cell line As4.1. ANGII decreased steady-state renin mRNA levels and prorenin secretion time and concentration (EC50 100 nmol/l) dependently. The effects of ANGII were blunted by the protein kinase C (PKC) inhibitor bisindolylmaleimide I and mimicked by the PKC activator phorbol 12-myristate-13-acetate (PMA) (EC50 10 nmol/l). ANGII also inhibited renin promoter activity PKC-dependently. The inhibitory sequences triggered by ANGII appear to reside within the first 2.9 kb in the 5'-flanking region of the mouse rent c gene but are not related to the two canonical activator protein-1 (AP-1) binding sites at positions -16 to -22 and -141 to -147. In summary, our data suggest that ANGII acts directly on renal juxtaglomerular cells to inhibit renin gene transcription through the PKC pathway. Since the PKC pathway can be activated by a variety of hormones it represents a powerful and probably rather important downstream pathway in the control of renin gene expression.

Item Type: Article
Uncontrolled Keywords: JUXTAGLOMERULAR CELLS; FEEDBACK-REGULATION; CHORIONIC CELLS; AS4.1 CELLS; CYCLIC-AMP; EXPRESSION; KIDNEY; INTERLEUKIN-1; SECRETION; PRORENIN; As4.1 cell line; Ren1c promoter; angiotensin II; protein kinase C; phorbol ester
Subjects: 500 Science > 570 Life sciences
600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz
Depositing User: Dr. Gernot Deinzer
Date Deposited: 19 Oct 2021 05:41
Last Modified: 19 Oct 2021 05:41
URI: https://pred.uni-regensburg.de/id/eprint/40135

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