Calcineurin mediates the angiotensin II-induced aldosterone synthesis in the adrenal glands by up-regulation of transcription of the CYP11B2 gene

Toshiyuki Yamashiro, Hideaki Kuge, Jin Zhang, Koichi Honke

Research output: Contribution to journalArticle

Abstract

Aldosterone synthesis in the zona glomerulosa of the adrenal gland is catalysed by aldosterone synthase (CYP11B2). The CYP11B2 expression is induced by angiotensin II (Ang II), mediated by increase of intracellular Ca 2+ level. Since calcineurin (CN) is an important mediator activated by Ca2+, we investigated the issue of whether CN is involved in the Ang II-induced CYP11B2 expression in human adrenocortical H295R cells. First, CN inhibitors, cyclosporine A (CysA) and tacrolimus (FK506) inhibited the Ang II-induced elevation of CYP11B2 mRNA level. Second, enforced expression of a constitutively active CN increased the CYP11B2 mRNA level. Third, depletion of CN by siRNA technique blocked the Ang II-induced elevation of CYP11B2 mRNA level. Fourth, in reporter assays using a luciferase gene connected to a 5′-flanking region (from-134 to +43 bp) of the hCYP11B2 gene, both CysA and FK506 inhibited the Ang II-mediated up-regulation of luciferase activity. Finally, activation of CN in living H295R cells following the Ang II treatment was confirmed using a fluorescence resonance energy transfer-based sensor. Taken together, we conclude that CN mediates the Ang II-induced aldosterone synthesis through up-regulation of the CYP11B2 transcription.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalJournal of Biochemistry
Volume148
Issue number1
DOIs
StatePublished - 2010

Fingerprint

Cytochrome P-450 CYP11B2
Calcineurin
Transcription
Adrenal Glands
Aldosterone
Angiotensin II
Up-Regulation
Genes
Tacrolimus
Luciferases
Messenger RNA
Cyclosporine
Zona Glomerulosa
Fluorescence Resonance Energy Transfer
5' Flanking Region
Small Interfering RNA
Assays
Chemical activation

Keywords

  • calciuum
  • cellular regulation
  • protein dephosphorylation
  • regulation
  • signal transduction
  • transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Medicine(all)

Cite this

Calcineurin mediates the angiotensin II-induced aldosterone synthesis in the adrenal glands by up-regulation of transcription of the CYP11B2 gene. / Yamashiro, Toshiyuki; Kuge, Hideaki; Zhang, Jin; Honke, Koichi.

In: Journal of Biochemistry, Vol. 148, No. 1, 2010, p. 115-123.

Research output: Contribution to journalArticle

Yamashiro, Toshiyuki ; Kuge, Hideaki ; Zhang, Jin ; Honke, Koichi. / Calcineurin mediates the angiotensin II-induced aldosterone synthesis in the adrenal glands by up-regulation of transcription of the CYP11B2 gene. In: Journal of Biochemistry. 2010 ; Vol. 148, No. 1. pp. 115-123.
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