TY - JOUR
T1 - Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells
AU - Matsuda, Ken
AU - Uruno, Akira
AU - Kogure, Naotaka
AU - Sugawara, Kaori
AU - Shimada, Hiroki
AU - Nezu, Masahiro
AU - Saito-Ito, Takako
AU - Iki, Yuko
AU - Kudo, Masataka
AU - Shimizu, Kyoko
AU - Sato, Ikuko
AU - Yoshikawa, Takeo
AU - Satoh, Fumitoshi
AU - Ito, Ryo
AU - Yokoyama, Atsushi
AU - Rainey, William E.
AU - Saito-Hakoda, Akiko
AU - Ito, Sadayoshi
AU - Sugawara, Akira
N1 - Funding Information:
This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 22591006 for A.S.), Grants-in-Aid from the Ministry of Health, Labor, and Welfare of Japan (for A.S.), and Research Grants from Smoking Research Foundation (for A.S.). We acknowledge Miki Nakamura B.S. and Rou Takahashi B.S. for helpful suggestions and experimental procedures.
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
KW - ARB
KW - Aldosterone
KW - CYP11B2
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U2 - 10.1016/j.mce.2013.12.004
DO - 10.1016/j.mce.2013.12.004
M3 - Article
C2 - 24333837
AN - SCOPUS:84891131019
SN - 0303-7207
VL - 383
SP - 60
EP - 68
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -