Soluble adenylyl cyclase: A novel player in cardiac hypertrophy induced by isoprenaline or pressure overload

Autor: Nicole Klein, Yury Ladilov, Kornelia Jaquet, Tippaporn Bualeong, Peter H Reusch, Rainer Meyer, Avinash Appukuttan, Ilona Schirmer, Heidi Budde, Andreas Mügge, Philip Steinwascher, Diana Cimiotti
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Physiology
lcsh:Medicine
Blood Pressure
Biochemistry
Vascular Medicine
Muscle hypertrophy
Adenylyl cyclase
chemistry.chemical_compound
Mice
Contractile Proteins
Medicine and Health Sciences
Post-Translational Modification
Phosphorylation
lcsh:Science
education.field_of_study
Multidisciplinary
biology
Cardiac muscle
Heart
Adrenergic beta-Agonists
Systolic Pressure
Enzymes
medicine.anatomical_structure
Physiological Parameters
Knockout mouse
Anatomy
Adenylyl Cyclase
medicine.drug
Research Article
Adenylyl Cyclases
medicine.medical_specialty
Cardiac Hypertrophy
Cardiology
Lyases
Cardiomegaly
CREB
Transfection
Research and Analysis Methods
03 medical and health sciences
Internal medicine
Isoprenaline
medicine
Pressure
Animals
education
Molecular Biology Techniques
Molecular Biology
Pressure overload
Body Weight
lcsh:R
Isoproterenol
Biology and Life Sciences
Proteins
Soluble adenylyl cyclase
Actins
Rats
Cytoskeletal Proteins
030104 developmental biology
Endocrinology
chemistry
biology.protein
Cardiovascular Anatomy
Enzymology
lcsh:Q
Zdroj: PLoS ONE, Vol 13, Iss 2, p e0192322 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: 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. Methods and results In isolated adult rat cardiomyocytes hypertrophy was induced by 24 h β1-adrenoceptor stimulation using isoprenaline (ISO) and a β2-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. Conclusion Soluble adenylyl cyclase might be a new pivotal player in the cardiac hypertrophic response either to long-term β1-adrenoceptor stimulation or to pressure overload.
Databáze: OpenAIRE
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