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

Ken Matsuda, Akira Uruno, Naotaka Kogure, Kaori Sugawara, Hiroki Shimada, Masahiro Nezu, Takako Saito-Ito, Yuko Iki, Masataka Kudo, Kyoko Shimizu, Ikuko Sato, Takeo Yoshikawa, Fumitoshi Satoh, Ryo Ito, Atsushi Yokoyama, William E. Rainey, Akiko Hakoda, Sadayoshi Ito, Akira Sugawara

研究成果: Article査読

6 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)60-68
ページ数9
ジャーナルMolecular and Cellular Endocrinology
383
1-2
DOI
出版ステータスPublished - 2013 12

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 内分泌学

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