Reactivation of the Mitosis-Promoting Factor in Postmitotic Cardiomyocytes
| Autor: | Lionel Wightman, Christian Weikert, Daniel A. Dätwyler, Ernst Wagner, Hans M. Eppenberger, Josef P. Magyar |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Histology
Cell cycle checkpoint Cell division Maturation-Promoting Factor Maturation promoting factor Cyclin B 030204 cardiovascular system & hematology Cell Line S Phase 03 medical and health sciences 0302 clinical medicine CDC2 Protein Kinase Animals Humans Myocytes Cardiac Cyclin B1 Phosphorylation Mitosis 030304 developmental biology 0303 health sciences Cyclin-dependent kinase 1 Arc (protein) biology Myocardium Cell Cycle G1 Phase Gene Transfer Techniques Gene Expression Regulation Developmental Cell Differentiation Heart Cell cycle Rats Cell biology Genes cdc biology.protein Female Anatomy |
| Zdroj: | Cells Tissues Organs. 175:61-71 |
| ISSN: | 1422-6421 1422-6405 |
| DOI: | 10.1159/000073750 |
| Popis: | Cardiomyocytes cease to divide shortly after birth and an irreversible cell cycle arrest is evident accompanied by the downregulation of cyclin-dependent kinase activities. To get a better understanding of the cardiac cell cycle and its regulation, the effect of functional recovery of the mitosis-promoting factor (MPF) consisting of cyclin B1 and the cyclin-dependent kinase Cdc2 was assessed in primary cultures of postmitotic ventricular adult rat cardiomyocytes (ARC). Gene transfer into ARC was achieved using the adenovirus-enhanced transferrinfection system that was characterized by the absence of cytotoxic events. Simultaneous ectopic expression of wild-type versions of cyclin B1 and Cdc2 was sufficient to induce MPF activity. Reestablished MPF resulted in a mitotic phenotype, marked by an abnormal condensation of the nuclei, histone H3 phosphorylation and variable degree of decay of the contractile apparatus. Although a complete cell division was not observed, the results provided conclusive evidence that cell cycle-related events in postmitotic cardiomyocytes could be triggered by genetic intervention downstream of the G1/S checkpoint. This will be of importance to design novel strategies to overcome the proliferation arrest in adult cardiomyocytes. |
| Databáze: | OpenAIRE |
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