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Mol Cell Endocrinol. 2014 Mar 5;383(1-2):60-8. doi: 10.1016/j.mce.2013.12.004. Epub 2013 Dec 12.

Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells.

Author information

  • 1Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
  • 2Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
  • 3Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
  • 4Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
  • 5Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-5622, USA.
  • 6Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: akiras2i@med.tohoku.ac.jp.

Abstract

We generated a stable H295R cell line expressing aldosterone synthase gene (CYP11B2) promoter/luciferase chimeric reporter construct that is highly sensitive to angiotensin II (AII) and potassium, and defined AII receptor blocker (ARB) effects. In the presence of AII, all ARBs suppressed AII-induced CYP11B2 transcription. However, telmisartan alone increased CYP11B2 transcription in the absence of AII. Telmisartan dose-dependently increased CYP11B2 transcription/mRNA expression and aldosterone secretion. Experiments using CYP11B2 promoter mutants indicated that the Ad5 element was responsible. Among transcription factors involved in the element, telmisartan significantly induced NGFIB/NURR1 expression. KN-93, a CaMK inhibitor, abrogated the telmisartan-mediated increase of CYP11B2 transcription/mRNA expression and NURR1 mRNA expression, but not NGFIB mRNA expression. NURR1 over-expression significantly augmented the telmisartan-mediated CYP11B2 transcription, while high-dose olmesartan did not affect it. Taken together, telmisartan may stimulate CYP11B2 transcription via NGFIB and the CaMK-mediated induction of NURR1 that activates the Ad5 element, independent of AII type 1 receptor.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

ARB; Aldosterone; CYP11B2

PMID:
24333837
[PubMed - in process]
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