Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/5221
Título
Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through p21 activation
Autor(es)
Aix, Esther CNIC | Gutierrez-Gutierrez, Oscar CNIC | Sanchez-Ferrer, Carlota CNIC | Aguado, Tania CNIC | Flores, Ignacio CNIC
Fecha de publicación
2016
Cita
J Cell Biol. 2016; 213(5):571-83
Idioma
Inglés
Tipo de documento
journal article
Resumen
The molecular mechanisms that drive mammalian cardiomyocytes out of the cell cycle soon after birth remain largely unknown. Here, we identify telomere dysfunction as a critical physiological signal for cardiomyocyte cell-cycle arrest. We show that telomerase activity and cardiomyocyte telomere length decrease sharply in wild-type mouse hearts after birth, resulting in cardiomyocytes with dysfunctional telomeres and anaphase bridges and positive for the cell-cycle arrest protein p21. We further show that premature telomere dysfunction pushes cardiomyocytes out of the cell cycle. Cardiomyocytes from telomerase-deficient mice with dysfunctional telomeres (G3 Terc(-/-)) show precocious development of anaphase-bridge formation, p21 up-regulation, and binucleation. In line with these findings, the cardiomyocyte proliferative response after cardiac injury was lost in G3 Terc(-/-) newborns but rescued in G3 Terc(-/-)/p21(-/-) mice. These results reveal telomere dysfunction as a crucial signal for cardiomyocyte cell-cycle arrest after birth and suggest interventions to augment the regeneration capacity of mammalian hearts.
Palabras clave
MOUSE HEART | TERMINAL TRANSFERASE | CARDIAC REGENERATION | OXIDATIVE STRESS | MAMMALIAN HEART | STEM-CELLS | PROLIFERATION | EXPRESSION | CANCER | MICE
Versión en línea
DOI
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