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Query: UMLS:C0020538 (
hypertension
)
170,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Aldosterone production is initiated by angiotensin II stimulation and activation of intracellular Ca
2+
signaling. In aldosterone-producing adenoma (APA) cells, the activation of intracellular Ca
2+
signaling is independent of the renin-angiotensin-aldosterone systems. The purpose of our study was to clarify molecular mechanisms of aldosterone production related to Ca
2+
signaling. Transcriptome analysis revealed that the
CALN1
gene encoding calneuron 1 had the strongest correlation with
CYP11B2
(aldosterone synthase) among genes encoding Ca
2+
-binding proteins in APA.
CALN1
modulation and synthetic or fluorescent compounds were used for functional studies in human adrenocortical carcinoma (HAC15) cells.
CALN1
expression was 4.4-fold higher in APAs than nonfunctioning adrenocortical adenomas.
CALN1
expression colocalized with CYP11B2 expression as investigated using immunohistochemistry in APA and zona glomerulosa of male rats fed by a low-salt diet.
CALN1
expression was detected in the endoplasmic reticulum (ER) by using GFP-fused
CALN1
, CellLight ER-RFP, and the corresponding antibodies.
CALN1
-overexpressing HAC15 cells showed increased Ca
2+
in the ER and cytosol fluorescence-based studies. Aldosterone production was potentiated in HAC15 cells by
CALN1
expression, and dose-responsive inhibition with TMB-8 showed that
CALN1
-mediated Ca
2+
storage in ER involved sarcoendoplasmic reticulum calcium transport ATPase. The silencing of
CALN1
decreased Ca
2+
in ER, and abrogated angiotensin II- or KCNJ5 T158A-mediated aldosterone production in HAC15 cells. Increased
CALN1
expression in APA was associated with elevated Ca
2+
storage in ER and aldosterone overproduction. Suppression of
CALN1
expression prevented angiotensin II- or KCNJ5 T158A-mediated aldosterone production in HAC15 cells, suggesting that
CALN1
is a potential therapeutic target for excess aldosterone production.
Hypertension
2018 01
PMID:Calneuron 1 Increased Ca
2+
in the Endoplasmic Reticulum and Aldosterone Production in Aldosterone-Producing Adenoma. 2910 91
