RGS2 inhibits β-adrenergic receptor-induced cardiomyocyte hypertrophy
Abstract
The chronic stimulation of certain G protein-coupled receptors promotes cardiomyocyte hypertrophy and thus plays a pivotal role in the development of human heart failure. The beta-adrenergic receptors (beta-AR) are unique among these in that they signal via Gs, whereas others, such as the alpha1-adrenergic (alpha1-AR) and endothelin-1 (ET-1) receptors, predominantly act through Gq. In this study, we investigated the potential role of regulator of G protein signalling 2 (RGS2) in modulating the hypertrophic effects of the beta-AR agonist isoproterenol (ISO) in rat neonatal ventricular cardiomyocytes. We found that ISO-induced hypertrophy in rat neonatal ventricular myocytes was accompanied by the selective upregulation of RGS2 mRNA, with little or no change in RGS1, RGS3, RGS4 or RGS5. The adenylyl cyclase activator forskolin had a similar effect suggesting that it was mediated through cAMP production. To study the role of RGS2 upregulation in beta-AR-dependent hypertrophy, cardiomyocytes were infected with adenovirus encoding RGS2 and assayed for cell growth, markers of hypertrophy, and beta-AR signalling. ISO-induced increases in cell surface area were virtually eliminated by the overexpression of RGS2, as were increases in alpha-skeletal actin and atrial natriuretic peptide. RGS2 overexpression also significantly attenuated ISO-induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Akt activation, which may account for, or contribute to, its observed antihypertrophic effects. In contrast, RGS2 overexpression significantly activated JNK MAP kinase, while decreasing the potency but not the maximal effect of ISO on cAMP accumulation. In conclusion, the present results suggest that RGS2 negatively regulates hypertrophy induced by beta-AR activation and thus may play a protective role in cardiac hypertrophy.
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Oxidative stress may modulate RGS2, which is part of the adrenergic receptors during conditioned fear response.
“In this way, since oxidative stress may be a molecular response to psychological stress, it might actually modulate the regulator of G-protein signalling 2 (RGS2) [194], which is a part of the adrenergic receptors during conditioned fear response.”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [194]
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- Authors
- Nunn, C., Zou, M.-X., Sobiesiak, A. J., Roy, A. A., Kirshenbaum, L. A., & Chidiac, P.
- Affiliations
- Western University (CA)
- St. Boniface Hospital (CA)
- Corresponding author
- Chidiac, Peter
- Venue
- Cellular Signalling
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 22
- Issue
- 8
- Pages
- 1231-1239
- ISSN
- 0898-6568 (ISSN-L)
- OpenAlex
- W2033577990
- Cited by
- 60
- References
- 38
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 8 · 2014: 6 · 2013: 3 · 2012: 5
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Signalling (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- RGS2, regulator of G protein signaling, beta-adrenergic receptors, cardiomyocyte hypertrophy, isoproterenol, cAMP signaling, Gs protein, ERK1/2, Akt, JNK MAP kinase, heart failure, neonatal cardiomyocytes, adenoviral overexpression
- MeSH terms
- Adrenergic beta-Agonists, Animals, Cells, Cultured, Heart Ventricles, Isoproterenol, Signal Transduction, Rats, Sprague-Dawley, Cyclic AMP-Dependent Protein Kinases, GTP-Binding Protein alpha Subunits, Gs, Endothelin-1, RGS Proteins, Myocytes, Cardiac, GTP-Binding Protein alpha Subunits, Gq-G11, Cell Enlargement, Rats
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