Korean J Intern Med.
1998 Jul;13(2):77-82.
Cell cycle regulators during human atrial development
- Affiliations
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- 1Institute of Cardiovascular Research, Chonbuk National University Medical School, Chonju, Korea.
- 2Department of Obstetrics, Chonbuk National University Medical School, Chonju, Korea.
- 3Department of Gynecology, Chonbuk National University Medical School, Chonju, Korea.
- 4Department of Cardiac Regeneration Group, Chonbuk National University Medical School, Chonju, Korea.
Abstract
OBJECTIVES
The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans. METHODS: Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery. Cyclin and CDK proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate. RESULTS: Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP1 protein increased markedly in the adult period, while p21CIP1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period. CONCLUSION: These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans.
MeSH Terms
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Adult
Age Factors
Animal
Blotting, Western
Cell Cycle
Cells, Cultured
Comparative Study
Cyclin A/analysis
Cyclin B/analysis
Cyclin D1/analysis
Cyclin E/analysis
Cyclin-Dependent Kinases/analysis*
Cyclins/analysis*
Female
Fetal Development
Heart Atrium/growth & development*
Heart Atrium/embryology
Heart Atrium/cytology*
Heart Atrium/chemistry
Human
Male
Middle Age
Myocardium/chemistry*
Rats
Rats, Sprague-Dawley
Substances: Cyclin D1
Substances: Cyclins
Substances: Cyclin-Dependent Kinases
Substances: Cyclin E
Substances: Cyclin B
Substances: Cyclin A
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