Voltage-gated calcium channels in the human adrenal and primary aldosteronism

被引:32
作者
Felizola, Saulo J. A. [1 ]
Maekawa, Takashi [1 ]
Nakamura, Yasuhiro [1 ]
Satoh, Fumitoshi [2 ]
Oho, Yoshikiyo [2 ]
Kikuchi, Kumi [2 ]
Aritomi, Shizuka [3 ]
Ikeda, Keiichi [4 ]
Yoshimura, Michihiro [5 ]
Tojo, Katsuyoshi [6 ]
Sasano, Hironobu [1 ]
机构
[1] Tohoku Univ, Grad Sch Med, Dept Pathol, Sendai, Miyagi 9808575, Japan
[2] Tohoku Univ Hosp, Div Nephrol Endocrinol & Vasc Med, Sendai, Miyagi, Japan
[3] Ajinomoto Co Inc, R&D Planning Dept, Kawasaki, Kanagawa, Japan
[4] Jikei Univ, Sch Med, Res Ctr Med Sci, Mol Cell Biol Div,Core Res Facil Basic Sci, Tokyo, Japan
[5] Jikei Univ, Sch Med, Dept Internal Med, Div Cardiol, Tokyo, Japan
[6] Jikei Univ, Kashiwa Hosp, Dept Internal Med, Div Diabet & Endocrinol, Tokyo, Japan
关键词
Calcium channel; Aldosterone; Adrenal cortex; Aldosterone producing adenoma; Immunohistochemistry; SOMATIC MUTATIONS; GLOMERULOSA CELLS; ESTROGEN-RECEPTOR; ANGIOTENSIN-II; CA2+ CHANNELS; K+; KCNJ5; BIOSYNTHESIS; EFONIDIPINE; EXPRESSION;
D O I
10.1016/j.jsbmb.2014.08.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Calcium channel blockers can efficiently be used in the treatment of primary aldosteronism (PA) related hypertension, but details on the localization of calcium channel (CC) in the human adrenal and its disorders, including PA, have remained unclear. Therefore, in this study we analyzed the known alpha subunits of L-, N- and T-type CCs in 74 adrenocortical aldosterone-producing adenomas (APA) and 16 cortisol-producing adenomas (CPA) using quantitative RT-PCR (qPCR). We also examined the status of L-(CaV1.2, CaV1.3), N-(CaV2.2) and T-(CaV3.2) CC subunits in five non-pathological adrenals (NA), five idiopathic hyperaldosteronism (IHA) cases, and 50 APA using immunohistochemistry. After qPCR evaluation, only CaV1.2, CaV1.3, CaV2.2, and CaV3.2 mRNA levels could be detected in APA and CPA. Among those, only CaV3.2 mRNA levels were significantly correlated with plasma aldosterone levels (P = 0.0031), CYP11B2 expression levels (P < 0.0001) and the presence of KCNJ5 mutations (P = 0.0019) in APA. The immunolocalization of CCs in NA and IHA was detected in the zona glomerulosa (ZG), with a predominance of CaV3.2 in APA. These findings suggest that different types of CC can be involved in calcium-related aldosterone biosynthesis. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:410 / 416
页数:7
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