Artery Research

Volume 25, Issue Supplement 1, December 2019, Pages S44 - S44

P2 Calcium Induced Intramitochondrial cAMP Signalling Enhances Aldosterone Secretion

Authors
Gergő Szanda*, Éva Wisniewski, Anikó Rajki, András Spät
Semmelweis University, Budapest, Hungary
*Corresponding author. Email: szgergo82@gmail.com
Corresponding Author
Gergő Szanda
Available Online 15 February 2020.
DOI
10.2991/artres.k.191224.037How to use a DOI?
Abstract

Elevation of plasma [K+] and [angiotensin II] (Ang II), two major physiological stimuli of adrenal zona glomerulosa cells, increase aldosterone production by triggering cytosolic Ca2+ signalling. Cytosolic Ca2+ signals are accompanied by mitochondrial Ca2+ elevations which further strengthen this steroidogenic response. It has recently been recognized that such mitochondrial Ca2+ signals activate the mitochondrial soluble adenylyl cyclase (sAC) thus evoking intramitochondrial (matrix) cAMP elevations during Ca2+ signalling. We hypothesised that this Ca2+ induced mitochondrial cAMP production, too, contributes to the hypersecretion of aldosterone. Using human adrenocortical H295R cells we found that silencing of sAC decreased mitochondrial cAMP production and, at the same time, decelerated Ca2+ accumulation by the organelle. On the other hand, inhibition of the mitochondrial phosphodiesterase (PDE2A) intensified matrix cAMP production and accelerated mitochondrial Ca2+ uptake. More importantly, both pharmacological inhibition and knock-down of sAC mitigate AngII-induced aldosterone production. Finally, overexpression of wild-type sAC within the mitochondrial matrix increased mitochondrial cAMP formation, accelerated mitochondrial Ca2+ uptake and, most prominently, potentiated aldosterone production as compared to the enzymatically inactive mutant enzyme. Altogether, Ca2+-induced mitochondrial cAMP signalling supports aldosterone production by favouring additional Ca2+ influx into the organelle. This positive feed-back loop may expedite the hormonal response when immediate hypersecretion of mineralocorticoids is crucial for cardiovascular compensation (e.g. exsiccation, blood loss).

Copyright
© 2019 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.
Open Access
This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

Journal
Artery Research
Volume-Issue
25 - Supplement 1
Pages
S44 - S44
Publication Date
2020/02/15
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.2991/artres.k.191224.037How to use a DOI?
Copyright
© 2019 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.
Open Access
This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

Cite this article

TY  - JOUR
AU  - Gergő Szanda
AU  - Éva Wisniewski
AU  - Anikó Rajki
AU  - András Spät
PY  - 2020
DA  - 2020/02/15
TI  - P2 Calcium Induced Intramitochondrial cAMP Signalling Enhances Aldosterone Secretion
JO  - Artery Research
SP  - S44
EP  - S44
VL  - 25
IS  - Supplement 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.191224.037
DO  - 10.2991/artres.k.191224.037
ID  - Szanda2020
ER  -