Role of G1 phase cyclins and cyclin-dependent kinases during cardiomyocyte hypertrophic growth in rats.
Cell cycle regulatory molecules are implicated in cardiomyocyte hypertrophy. We have investigated protein expression of cyclins A, D1-3, and E and cyclin-dependent kinases (CDKs) 2, 4, 5, and 6 in left ventricular (LV) tissues during the development of LV hypertrophy in rats following aortic constriction (AC). Compared with their expression in sham-operated controls (SH), expression of cyclins D2 and D3 and of CDK4 and CDK6 increased significantly from day 3 to day 21 after AC concomitant with increased LV mass. However, no significant difference was observed for CDK2 or CDK5. Cyclins A, D1, and E were undetectable. In vitro kinase activities of CDK4 and CDK6 increased approximately 70% from day 7 to day 14 in AC myocytes compared with SH myocytes (P < 0.03). Fluorescence-activated cell sorter analysis revealed a G0/G1 to G2/M phase progression in AC myocyte nuclei (22.0 +/- 1.1% in G2/M) by day 7 postoperation compared with progression in SH myocyte nuclei (14.0 +/- 0.8% in G2/M; P < 0.01). Thus an upregulation of certain cell cycle regulators is associated with cardiomyocyte hypertrophy.
Li
J M
JM
Cardiovascular Cellular and Molecular Biology, Cardiovascular Research, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
Poolman
R A
RA
Brooks
G
G
D016475:3T3 Cells; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D056742:Cyclin D2; D056743:Cyclin D3; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D007163:Immunosorbent Techniques; D008297:Male; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase / Q000502:physiology; D014661:Vasoconstriction
C486196:Ccnd2 protein, mouse; C486197:Ccnd2 protein, rat; C534697:Ccnd3 protein, mouse; C534698:Ccnd3 protein, rat; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; C495902:Cdk4 protein, mouse; C495903:Cdk4 protein, rat; C495912:Cdk6 protein, mouse; C495913:Cdk6 protein, rat; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases