Calpain-10 activity underlies angiotensin II-induced aldosterone production in an adrenal glomerulosa cell model

Mutsa Seremwe, Rick G. Schnellmann, Wendy B. Bollag

Research output: Contribution to journalArticle

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Abstract

Aldosterone is a steroid hormone important in the regulation of blood pressure. Aberrant production of aldosterone results in the development and progression of diseases including hypertension and congestive heart failure; therefore, a complete understanding of aldosterone production is important for developing more effective treatments. Angiotensin II (AngII) regulates steroidogenesis, in part through its ability to increase intracellular calcium levels. Calcium can activate calpains, proteases classified as typical or atypical based on the presence or absence of penta-EF-hands, which are involved in various cellular responses. We hypothesized that calpain, in particular calpain-10, is activated by AngII in adrenal glomerulosa cells and underlies aldosterone production. Our studies showed that pan-calpain inhibitors reduced AngII-induced aldosterone production in 2 adrenal glomerulosa cell models, primary bovine zona glomerulosa and human adrenocortical carcinoma (HAC15) cells, as well as CYP11B2 expression in the HAC15 cells. Although AngII induced calpain activation in these cells, typical calpain inhibitors had no effect on AngIIelicited aldosterone production, suggesting a lack of involvement of classical calpains in this process. However, an inhibitor of the atypical calpain, calpain-10, decreased AngII-induced aldosterone production. Consistent with this result, small interfering RNA (siRNA)-mediated knockdown of calpain-10 inhibited aldosterone production and CYP11B2 expression, whereas adenovirusmediated overexpression of calpain-10 resulted in increased AngII-induced aldosterone production. Our results indicate that AngII-induced activation of calpain-10 in glomerulosa cells underlies aldosterone production and identify calpain-10 or its downstream pathways as potential targets for the development of drug therapies for the treatment of hypertension.

Original languageEnglish (US)
Pages (from-to)2138-2149
Number of pages12
JournalEndocrinology
Volume156
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Zona Glomerulosa
Aldosterone
Angiotensin II
Calpain
Cytochrome P-450 CYP11B2
calpain 10
Hypertension
Adrenocortical Carcinoma
Calcium
EF Hand Motifs
Rubiaceae
Small Interfering RNA
Disease Progression
Peptide Hydrolases
Heart Failure
Steroids
Hormones
Blood Pressure

ASJC Scopus subject areas

  • Endocrinology

Cite this

Calpain-10 activity underlies angiotensin II-induced aldosterone production in an adrenal glomerulosa cell model. / Seremwe, Mutsa; Schnellmann, Rick G.; Bollag, Wendy B.

In: Endocrinology, Vol. 156, No. 6, 01.06.2015, p. 2138-2149.

Research output: Contribution to journalArticle

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