PMID:20362664

Citation	Nunn, C, Zou, MX, Sobiesiak, AJ, Roy, AA, Kirshenbaum, LA and Chidiac, P (2010) RGS2 inhibits beta-adrenergic receptor-induced cardiomyocyte hypertrophy. Cell. Signal. 22:1231-9
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.
Links	PubMed Online version:10.1016/j.cellsig.2010.03.015
Keywords	Adrenergic beta-Agonists/pharmacology; Animals; Cell Enlargement; Cells, Cultured; Cyclic AMP-Dependent Protein Kinases/metabolism; Endothelin-1/pharmacology; GTP-Binding Protein alpha Subunits, Gq-G11/metabolism; GTP-Binding Protein alpha Subunits, Gs/metabolism; Heart Ventricles/cytology; Heart Ventricles/growth & development; Isoproterenol/pharmacology; Myocytes, Cardiac/cytology; Myocytes, Cardiac/enzymology; Myocytes, Cardiac/metabolism; RGS Proteins/metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:RGS2		GO:0071878: negative regulation of adrenergic receptor signaling pathway	ECO:0000315:		P		Figure 6: RGS2 overexpression leads to a reduction in cAMP accumulation in rat neonatal ventricular cardiomyocytes.	complete
RAT:RGS2		GO:0071875: adrenergic receptor signaling pathway	ECO:0000314:		P		Figure 1: Activation of B-AR induces RGS expression in cultured cardiomyocytes	complete
RAT:RGS2		GO:0010614: negative regulation of cardiac muscle hypertrophy	ECO:0000315:		P		Figure 4+5: RGS2 overexpression attenuates ISO-induced (B-AR) cardiomyoctye hypertrophy and hypertrophic gene expression.	complete
RAT:RGS2		GO:0043405: regulation of MAP kinase activity	ECO:0000314:		P		Figurre 7: Immunoblots show that RGS2 decreases ERK phosphorylation (a) and increases JNK phosphorylation (B) - part of MAP kinase pathway.	complete
RAT:RGS2		GO:0051896: regulation of protein kinase B signaling cascade	ECO:0000314:		P		Figure 8: Immunoblots show thatRGS2 limits signalling leading to Akt phosphorylation in cardiomyocytes	complete

References

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