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Título

The thyroid hormone receptor β induces DNA damage and premature senescence

Autor Zambrano, Alberto ; García-Carpizo, Verónica ; Gallardo, M. Esther ; Villamuera, Raquel; Gómez-Ferrería, María Ana ; Pascual, Ángel ; Buisine, Nicolas; Sachs, Laurent M.; Garesse, Rafael ; Aranda, Ana
Fecha de publicación 2014
EditorRockefeller University Press
Citación Journal of Cell Biology 204(1): 129-146 (2014)
ResumenThere 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. © 2014 Zambrano et al.
Descripción This article is distributed under the terms of a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license).
Versión del editorhttp://dx.doi.org/10.1083/jcb.201305084
URI http://hdl.handle.net/10261/103757
DOI10.1083/jcb.201305084
Identificadoresdoi: 10.1083/jcb.201305084
issn: 0021-9525
e-issn: 1540-8140
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