Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells
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- 作者：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 Saito-Hakoda ; Sadayoshi Ito ; Akira Sugawara
- 关键词：AII ; angiotensin II ; ARB ; AII receptor blocker ; RAAS ; renin&ndash ; angiotensin&ndash ; aldosterone system ; PPAR ; peroxisome proliferator-activated receptor ; CaMK ; Ca2+/calmodulin-dependent kinase ; NGFIB ; nerve growth factor-induced clone B ; NURR1 ; Nur-related factor 1
- 刊名：Molecular and Cellular Endocrinology
- 出版年：5 March, 2014
- 年：2014
- 卷：383
- 期：1-2
- 页码：60-68
- 全文大小：1145 K
文摘
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.