Cell cycle regulators during human atrial development.
- Author:
Won Ho KIM
1
;
Chan Uhng JOO
;
Ja Hong KU
;
Chul Hee RYU
;
Keum Nim KOH
;
Gou Young KOH
;
Jae Ki KO
Author Information
1. Institute of Cardiovascular Research, Chonbuk National University Medical School, Chonju, Korea.
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- MeSH:
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
- From:The Korean Journal of Internal Medicine
1998;13(2):77-82
- CountryRepublic of Korea
- Language:English
-
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.