title: Myocardial expression and redistribution of GRKs in hypertensive hypertrophy and failure.
abstract: G-protein-coupled receptor kinases (GRKs) are involved in cardiac hypertrophy and failure. But their temporal expression and cellular localization during the development of hypertrophy and its transition to failure remains to be investigated. In this study, we determined the expression and subcellular distribution of GRK2, GRK3, GRK5, and GRK6 in cardiac myocytes of 2- to 24-month-old spontaneously hypertensive heart failure (SHHF) rats. GRK2 increased in the intercalated disks in 6-, 12-, and 24-month-old SHHF rats, although total expression remained relatively constant from 2 to 24 months in both SHHF and normotensive rats. GRK3 expression progressively increased in 6-, 12-, and 24-month-old SHHF rats and was significantly higher than in age-matched controls. Immunolabeling of GRK3 showed a typical pattern of cross-striations that colocalized with alpha-actinin and G(alphas) at Z-lines in both SHHF and control rats. GRK5 expression showed no change from 2 to 24 months in both SHHF and normotensive rats. Confocal analysis revealed nuclear translocation of GRK5 in myocytes of SHHF rats. GRK6 had a striated pattern colocalized with alpha-actinin at Z-lines in the cytoplasm and was also present in the intercalated disks of cardiac myocytes from both SHHF and control rats. GRK6 expression increased in 12- and 24-month-old SHHF rats and was significantly higher than in age-matched controls. GRK6 labeling was reduced at the intercalated disks, but increased in the cytoplasm of cardiac myocytes from SHHF rats compared to age-matched controls. The increased expression of GRK3 and GRK6 and subcellular redistribution of GRK2, GRK5, and GRK6 in SHHF rats may be involved in abnormal remodeling of cardiac myocytes in hypertensive hypertrophy and failure.
authors.affiliation: South Dakota Health Research Foundation-Cardiovascular Research Institute, University of South Dakota, 1100 East 21st Street, Sioux Falls, SD 57105, USA.
authors.forename: Xian Ping
authors.initials: XP
authors.lastname: Yi
authors.forename: Jibin
authors.initials: J
authors.lastname: Zhou
authors.forename: Justin
authors.initials: J
authors.lastname: Baker
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wang
authors.forename: A Martin
authors.initials: AM
authors.lastname: Gerdes
authors.forename: Faqian
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006333:Heart Failure / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018613:Microscopy, Confocal; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled