Essential roles for G1 cyclin-dependent kinase activity in development of cardiomyocyte hypertrophy

• Published in: American journal of physiology. Heart and circulatory physiology 1998-12, Vol.275 (6), p.H2036
• Main Authors: Tamamori, Mimi, Ito, Hiroshi, Hiroe, Michiaki, Terada, Yoshio, Marumo, Fumiaki, Ikeda, Masa-Aki
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.6.h2036

1  Second Department of Internal Medicine and 2  Department of Developmental Biology, Graduate School of Dentistry, Tokyo Medical and Dental University, Tokyo 113, Japan 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 G 1 cyclins and cyclin-dependent kinase (CDK) activity in proliferating cells. We sought to determine whether G 1 CDK activity is involved in the hypertrophy of rat neonatal cardiomyocytes in culture. We show that serum stimulation promoted the G 1 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 -actin and atrial natriuretic factor, genetic markers of cardiac hypertrophy. These results suggest that the G 1 CDK 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. terminal differentiation; cell cycle regulators