The thyroid hormone receptor β induces DNA damage and premature senescence. [artículo]
Por: Garesse, Rafael [Instituto de Investigación i+12].
Colaborador(es): Instituto de Investigación imas12.
Tipo de material: ArtículoEditor: The Journal of cell biology, 2014Descripción: 204(1):129-46.Recursos en línea: Solicitar documento Resumen: There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate-activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double-strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism.Tipo de ítem | Ubicación actual | Signatura | Estado | Fecha de vencimiento |
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Artículo | PC16650 (Navegar estantería) | Disponible |
Formato Vancouver:
Zambrano A, García Carpizo V, Gallardo ME, Villamuera R, Gómez Ferrería MA, Pascual A et al.The thyroid hormone receptor β induces DNA damage and premature senescence. J Cell Biol. 2014 Jan 6;204(1):129-46.
PMID: 24395638
PMC3882795
Contiene 66 referencias
There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate-activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double-strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism.
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