Your browser doesn't support javascript.
loading
Differential Role of G Protein-Coupled Receptor Kinase 5 in Physiological Versus Pathological Cardiac Hypertrophy.
Traynham, Christopher J; Cannavo, Alessandro; Zhou, Yan; Vouga, Alexandre G; Woodall, Benjamin P; Hullmann, Jonathan; Ibetti, Jessica; Gold, Jessica I; Chuprun, J Kurt; Gao, Erhe; Koch, Walter J.
Affiliation
  • Traynham CJ; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Cannavo A; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Zhou Y; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Vouga AG; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Woodall BP; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Hullmann J; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Ibetti J; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Gold JI; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Chuprun JK; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Gao E; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
  • Koch WJ; From the Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA (C.J.T., A.C., A.G.V., B.P.W., J.H., J.I., J.I.G., J.K.C., E.G., W.J.K.); and Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA (Y.Z.
Circ Res ; 117(12): 1001-12, 2015 Dec 04.
Article in En | MEDLINE | ID: mdl-26515328
RATIONALE: G protein-coupled receptor kinases (GRKs) are dynamic regulators of cellular signaling. GRK5 is highly expressed within myocardium and is upregulated in heart failure. Although GRK5 is a critical regulator of cardiac G protein-coupled receptor signaling, recent data has uncovered noncanonical activity of GRK5 within nuclei that plays a key role in pathological hypertrophy. Targeted cardiac elevation of GRK5 in mice leads to exaggerated hypertrophy and early heart failure after transverse aortic constriction (TAC) because of GRK5 nuclear accumulation. OBJECTIVE: In this study, we investigated the role of GRK5 in physiological, swimming-induced hypertrophy (SIH). METHODS AND RESULTS: Cardiac-specific GRK5 transgenic mice and nontransgenic littermate control mice were subjected to a 21-day high-intensity swim protocol (or no swim sham controls). SIH and specific molecular and genetic indices of physiological hypertrophy were assessed, including nuclear localization of GRK5, and compared with TAC. Unlike after TAC, swim-trained transgenic GRK5 and nontransgenic littermate control mice exhibited similar increases in cardiac growth. Mechanistically, SIH did not lead to GRK5 nuclear accumulation, which was confirmed in vitro as insulin-like growth factor-1, a known mediator of physiological hypertrophy, was unable to induce GRK5 nuclear translocation in myocytes. We found specific patterns of altered gene expression between TAC and SIH with GRK5 overexpression. Further, SIH in post-TAC transgenic GRK5 mice was able to preserve cardiac function. CONCLUSIONS: These data suggest that although nuclear-localized GRK5 is a pathological mediator after stress, this noncanonical nuclear activity of GRK5 is not induced during physiological hypertrophy.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cardiomegaly / Myocytes, Cardiac / G-Protein-Coupled Receptor Kinase 5 Limits: Animals Language: En Journal: Circ Res Year: 2015 Document type: Article Country of publication: United States
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cardiomegaly / Myocytes, Cardiac / G-Protein-Coupled Receptor Kinase 5 Limits: Animals Language: En Journal: Circ Res Year: 2015 Document type: Article Country of publication: United States