Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts

M. Yoshizumi, W. S. Lee, C. M. Hsieh, J. C. Tsai, J. Li, M. A. Perrella, C. Patterson, W. O. Endege, R. Schlegel, M. E. Lee

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Abstract

The regulated expression of cyclins controls the cell cycle. Because cardiomyocytes in adult mammals withdraw permanently from the cell cycle and thus cannot regenerate after injury, we examined cyclin expression during development by comparing cyclin A-E mRNA levels in fetal and adult human hearts. Cyclin B mRNA was detectable in adult hearts, although at a level markedly lower than that in fetal hearts. Levels of cyclin C, D1, D2, D3, and E mRNA were essentially identical in the two groups. In contrast, cyclin A mRNA was undetectable in adult hearts whereas cyclin A mRNA and protein were readily detectable in fetal hearts and cardiomyocytes, respectively. We then measured cyclin A mRNA and protein levels in rat hearts at four stages of development (fetal and 2, 14, and 28 d). Cyclin A mRNA and protein levels decreased quickly after birth (to 37% at day 2) and became undetectable within 14 d, an observation consistent with reports that cardiomyocytes stop replicating in rats by the second to third postnatal week. This disappearance of cyclin A gene expression in human and rat hearts at the time cardiomyocytes become terminally differentiated suggests that cyclin A downregulation is important in the permanent withdrawal of cardiomyocytes from the cell cycle.

Original languageEnglish
Pages (from-to)2275-2280
Number of pages6
JournalJournal of Clinical Investigation
Volume95
Issue number5
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Cyclin A
Cardiac Myocytes
Cell Cycle
Messenger RNA
Fetal Heart
Cyclins
Cyclin C
Cyclin B
Cyclin E
Proteins
Cyclin D1
Fetal Development
Cell Cycle Checkpoints
Mammals
Down-Regulation
Observation
Parturition
Gene Expression
Wounds and Injuries

Keywords

  • cardiomyocytes
  • cell cycle
  • cyclins
  • gene regulation
  • heart

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts. / Yoshizumi, M.; Lee, W. S.; Hsieh, C. M.; Tsai, J. C.; Li, J.; Perrella, M. A.; Patterson, C.; Endege, W. O.; Schlegel, R.; Lee, M. E.

In: Journal of Clinical Investigation, Vol. 95, No. 5, 1995, p. 2275-2280.

Research output: Contribution to journalArticle

Yoshizumi, M, Lee, WS, Hsieh, CM, Tsai, JC, Li, J, Perrella, MA, Patterson, C, Endege, WO, Schlegel, R & Lee, ME 1995, 'Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts', Journal of Clinical Investigation, vol. 95, no. 5, pp. 2275-2280.
Yoshizumi, M. ; Lee, W. S. ; Hsieh, C. M. ; Tsai, J. C. ; Li, J. ; Perrella, M. A. ; Patterson, C. ; Endege, W. O. ; Schlegel, R. ; Lee, M. E. / Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 5. pp. 2275-2280.
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