Essential roles for G1cyclin-dependent kinase activity in development of cardiomyocyte hypertrophy

M Tamamori, H Ito, M Hiroe, Y Terada… - American Journal …, 1998 - journals.physiology.org
M Tamamori, H Ito, M Hiroe, Y Terada, F Marumo, MA Ikeda
American Journal of Physiology-Heart and Circulatory Physiology, 1998journals.physiology.org
Although cardiomyocytes undergo terminal differentiation soon after birth, irreversibly
withdrawing from the cell cycle, growth stimulation induces cell hypertrophy. Such growth
stimulation is also responsible for the upregulation of G1 cyclins and cyclin-dependent
kinase (CDK) activity in proliferating cells. We sought to determine whether G1 CDK activity
is involved in the hypertrophy of rat neonatal cardiomyocytes in culture. We show that serum
stimulation promoted the G1 CDK activity without induction of DNA synthesis in …
Although cardiomyocytes undergo terminal differentiation soon after birth, irreversibly withdrawing from the cell cycle, growth stimulation induces cell hypertrophy. Such growth stimulation is also responsible for the upregulation of G1 cyclins and cyclin-dependent kinase (CDK) activity in proliferating cells. We sought to determine whether G1 CDK activity is involved in the hypertrophy of rat neonatal cardiomyocytes in culture. We show that serum stimulation promoted the G1 CDK activity without induction of DNA synthesis in cardiomyocytes. Furthermore, overexpression of CDK inhibitors p16 INK4a and p21 CIP1/WAF1 by use of the adenovirus vector effectively prevented cell enlargement and depressed serum-induced protein synthesis and expression of skeletal α-actin and atrial natriuretic factor, genetic markers of cardiac hypertrophy. These results suggest that the G1CDK activity promoted by serum stimulation is required for the induction of cardiomyocyte hypertrophy and provide novel evidence for understanding the regulation of cardiac hypertrophy by cell cycle regulators.
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