The thyroid hormone receptor β induces DNA damage and premature senescence
Entity
Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)Publisher
The Rockefeller University PressDate
2014-01-06Citation
10.1083/jcb.201305084
Journal Cell Biology 204.1 (2014): 129-146
ISSN
0021-9525 (print); 1540-8140 (online)DOI
10.1083/jcb.201305084Funded by
This work was supported by grants from Ministerio de Economía y Competitividad (BFU2011-28958 to A. Aranda and SAF2009-11150 to A. Pascual), from the Instituto de Salud Carlos III (RD012/0036/0030 to A. Aranda; and PI 07/0167 and PI 10/0703 to R. Garesse), from the Comunidad de Madrid (S2011/BMD-2328 TIRONET to A. Aranda), and European Union grant project CRESCENDO (FP6-018652 to A. Aranda and L.M. Sachs).Project
Comunidad de Madrid. S2010/BMD-2328/TIRONETEditor's Version
http://dx.doi.org/10.1083/jcb.201305084Subjects
Thyroid hormone; DNA; Damage; Biología y Biomedicina / BiologíaRights
© 2014 Zambrano et al.
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional.
Abstract
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
Files in this item
Google Scholar:Zambrano, Alberto K.
-
García-Carpizo, Verónica
-
Gallardo, María Esther
-
Villamuera, Raquel
-
Gómez-Ferrería, María Ana
-
Pascual, Angel
-
Buisine, Nicolas
-
Sachs, Laurent M.
-
Garesse Alarcón, Rafael
-
Aranda, Ana
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.