Expression of cyclin D1 and CDK4 causes hypertrophic growth of cardiomyocytes in culture: A possible implication for cardiac hypertrophy

Mimi Tamamori-Adachi, Hiroshi Ito, Kiyoshi Nobori, Kentaro Hayashida, Junya Kawauchi, Susumu Adachi, Masa Aki Ikeda, Shigetaka Kitajima

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28 Citations (Scopus)

Abstract

Differentiated cardiomyocytes have little capacity to proliferate and show the hypertrophic growth in response to α1-adrenergic stimuli via the Ras/MEK pathway. In this study, we investigated a role of cyclin D1 and CDK4, a positive regulator of cell cycle, in cultured neonatal rat cardiomyocyte hypertrophy. D-type cyclins including cyclin D1 were induced in cells stimulated by phenylephrine. This induction was inhibited by MEK inhibitor PD98059 and the dominant negative RasN17, but mimicked by expression of the constitutive active Ras61L. Over-expression of cyclin D1 and CDK4 using adenovirus gene transfer caused the hypertrophic growth of cardiomyocytes, as evidenced by an increase of the cell size as well as the amount of cellular protein and its rate of synthesis. However, the cyclin D1/CDK4 kinase activity was not up-regulated in cells treated by hypertrophic stimuli or in cells over-expressing the cyclin D1 and CDK4. Furthermore, a CDK inhibitor, p16, did not inhibit the hypertrophic growth of cardiomyocytes. These results clearly indicated that cyclin D1 and CDK4 have a role in hypertrophic growth of cardiomyocytes through a novel mechanism(s) which appears not to be related to its activity required for cell cycle progression.

Original languageEnglish
Pages (from-to)274-280
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume296
Issue number2
DOIs
Publication statusPublished - 2002
Externally publishedYes

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Keywords

  • Cardiomyocyte
  • CDK4
  • Cell cycle
  • Cyclin D1
  • Hypertrophy
  • MEK
  • Phenylephrine
  • Ras

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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