Soluble adenylyl cyclase

  • \(\bf Aims\) In contrast to the membrane bound adenylyl cyclases, the soluble adenylyl cyclase (sAC) is activated by bicarbonate and divalent ions including calcium. sAC is located in the cytosol, nuclei and mitochondria of several tissues including cardiac muscle. However, its role in cardiac pathology is poorly understood. Here we investigate whether sAC is involved in hypertrophic growth using two different model systems. \(\textbf {Methods and results}\) In isolated adult rat cardiomyocytes hypertrophy was induced by 24 h \(\beta_{1}\)-adrenoceptor stimulation using isoprenaline (ISO) and a \(\beta_{2}\)-adrenoceptor antagonist (ICI118,551). To monitor hypertrophy cell size along with RNA/DNA- and protein/DNA ratios as well as the expression level of α-skeletal actin were analyzed. sAC activity was suppressed either by treatment with its specific inhibitor KH7 or by knockdown. Both pharmacological inhibition and knockdown blunted hypertrophic growth and reduced expression levels of α-skeletal actin in ISO/ICI treated rat cardiomyocytes. To analyze the underlying cellular mechanism expression levels of phosphorylated CREB, B-Raf and Erk1/2 were examined by western blot. The results suggest the involvement of B-Raf, but not of Erk or CREB in the pro-hypertrophic action of sAC. In wild type and sAC knockout mice pressure overload was induced by transverse aortic constriction. Hemodynamics, heart weight and the expression level of the atrial natriuretic peptide were analyzed. In accordance, transverse aortic constriction failed to induce hypertrophy in sAC knockout mice. Mechanistic analysis revealed a potential role of Erk1/2 in TAC-induced hypertrophy. \(\bf Conclusion\) Soluble adenylyl cyclase might be a new pivotal player in the cardiac hypertrophic response either to long-term \(\beta_{1}\)-adrenoceptor stimulation or to pressure overload.

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Metadaten
Author:Ilona SchirmerGND, Tippaporn BualeongGND, Heidi BuddeGND, Diana CimiottiORCiDGND, Avinash AppukuttanGND, Nicole KleinGND, Philip SteinwascherGND, Hans-Peter ReuschGND, Andreas MüggeORCiDGND, Rainer MeyerGND, Yuri LadilovGND, Kornelia JaquetGND
URN:urn:nbn:de:hbz:294-73531
DOI:https://doi.org/10.1371/journal.pone.0192322
Parent Title (English):PLoS ONE
Subtitle (English):a novel player in cardiac hypertrophy induced by isoprenaline or pressure overload
Publisher:Public Library of Science
Place of publication:San Francisco
Document Type:Article
Language:English
Date of Publication (online):2020/07/17
Date of first Publication:2018/02/21
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Volume:13
Issue:2, Artikel e0192322
First Page:e0192322-1
Last Page:e0192322-17
Institutes/Facilities:Institut für Biochemie und Pathobiochemie, Abteilung für Molekulare Zellbiologie
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International