Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure-prone rats.
Gprotein-coupled receptor kinases (GRKs) are known to be involved in the development of cardiac hypertrophy. Their exact role and subcellular distribution during cardiac hypertrophy and failure remain to be elucidated. We examined expression and subcellular distribution of GRK2 and GRK5 in the left ventricle of female spontaneously hypertensive heart failure (SHHF) rats at 6 months of age using Western blots and fluorescent confocal microscopy. GRK2 was expressed mainly in the Triton X-100 soluble fraction in the left ventricle with similar expression levels between SHHF and age-matched Wistar-Kyoto (WKY) rats. GRK2 had a striated pattern which colocalized with sarcomeric alpha-actinin and G protein in both SHHF and WKY rat myocytes and specifically accumulated in the intercalated disks of myocytes from SHHF but not WKY rats. GRK5 was expressed in both the Triton X-100 soluble fraction and Triton X-100 insoluble fraction in the left ventricle with similar expression levels between SHHF and WKY rats. GRK5 distributed diffusely in the cytoplasm in both SHHF and WKY rat myocytes and specifically accumulated in the nucleus of myocytes from SHHF but not WKY rats. GRK5 colocalized with coilin, the major component of the nuclear substructure involved in RNA synthesis and processing. The results suggest different roles for GRK2 and GRK5 in G-protein signaling and RNA biogenesis. Subcellular redistribution of GRK2 and GRK5 may be involved in cardiac hypertrophy resulting from chronic hypertension.
Yi
Xian Ping
XP
South Dakota Health Research Foundation-Cardiovascular Research Institute, Department of Laboratory Medicine and Pathology, University of South Dakota School of Medicine, Sioux Falls, SD 57105, USA.
Gerdes
A Martin
AM
Li
Faqian
F
D000185:Actinin / Q000032:analysis; D021581:Active Transport, Cell Nucleus; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology / Q000209:etiology; D002467:Cell Nucleus / Q000201:enzymology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis* / Q000378:metabolism; D005260:Female; D054774:G-Protein-Coupled Receptor Kinase 5; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000032:analysis; D006333:Heart Failure / Q000201:enzymology; D006352:Heart Ventricles / Q000201:enzymology; D006973:Hypertension / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D009687:Nuclear Proteins / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012518:Sarcomeres / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051552:beta-Adrenergic Receptor Kinases
D009687:Nuclear Proteins; D000185:Actinin; C068921:p80-coilin; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D054774:G-Protein-Coupled Receptor Kinase 5; C517897:Grk5 protein, rat; D019205:GTP-Binding Protein alpha Subunits, Gs; D013755:Tetradecanoylphorbol Acetate