Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase.

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Condon JC, Pezzi V, Drummond BM, Yin S, Rainey WE

Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase.

Endocrinology. 2002 Sep;143(9):3651-7.

PubMed ID

12193581 [ View in PubMed

]

Abstract

Aldosterone synthase (CYP11B2) is expressed in the adrenal glomerulosa and controls the capacity of the adrenal glomerulosa to produce aldosterone. Herein, human NCI-H295R (H295R) adrenocortical cells were used to define the calcium-dependent mechanisms regulating CYP11B2 gene transcription using reporter constructs containing CYP11B2 gene 5'-flanking DNA. Treatment of H295R cells with calcium/calmodulin-dependent protein kinase (CaMK) inhibitor (KN93) or calmodulin inhibitor (calmidazolium) blocked angiotensin II and potassium (K(+)) stimulation of CYP11B2 reporter gene expression. To determine which CaMK regulates CYP11B2, vectors containing the complete coding sequences for CaMKI, CaMKII, and CaMKIV were transfected with the CYP11B2 reporter construct. CaMKI augmented reporter expression when cellular calcium was elevated by ionomycin, whereas CaMKIV had a small effect, and CaMKII had no effect. To further study the role of CaMKs, constitutively active forms of CaMKI (CaMKI-295), II (CaMKII-290), and IV (CaMKIV-313) were transfected with CYP11B2 reporter constructs. CaMKI-295 and, to a lesser degree, CaMKIV-313 were able to stimulated reporter activity. Mutational analysis of the 5'-flanking region of CYP11B2 revealed that a cAMP regulatory element (-71/-64) was necessary for CaMKI induction of reporter gene activity. CaMKI expression was shown in adrenal cortex and H295R cells using immunohistochemistry and Western and Northern analyses. These findings suggest that CaMKI is involved in angiotensin II and K(+) stimulation of CYP11B2 transcription and, therefore, the capacity of the adrenal to produce aldosterone.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
Calcium/calmodulin-dependent protein kinase type 1	Q14012	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Potassium cation	Approved Investigational	CYP11B2	1585	upregulated	Potassium results in increased expression of CYP11B2 mRNA	8q24.3