2026-07-21T14:57:56Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/129462025-06-13T09:42:53Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_19605col_20.500.12105_19617
Repisalud
author
Prieto, Ignacio
author
Zambrano, Alberto
author
Laso, Javier
author
Aranda, Ana
author
Samper, Enrique
author
Monsalve, María
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. H2020
funder
Instituto de Salud Carlos III
2021-05-12T12:25:15Z
2021-05-12T12:25:15Z
2019
Free Radic Biol Med. 2019 Jul;138:23-32.
10.1016/j.freeradbiomed.2019.04.015
1873-4596
Free Radical Biology & Medicine
31029787
http://hdl.handle.net/20.500.12105/12946
Aims: Oxidative stress is known to induce early replicative senescence. Senescence has been proposed to work as a barrier to immortalization and tumor development. Here, we aimed to evaluate the impact of the loss of peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α), a master regulator of oxidative metabolism and mitochondrial reactive oxygen species (ROS) generation, on replicative senescence and immortalization in mouse embryonic fibroblasts (MEFs). Results: We found that primary MEFs lacking PGC-1α showed higher levels of ROS than wild-type MEFs at all cell passages tested. The elevated production of ROS was associated with higher levels of oxidative DNA damage and the increased formation of DNA double-strand breaks. Evaluation of the induction of DNA repair systems in response to γ-radiation indicated that the loss of PGC-1α also resulted in a small but significant reduction in their activity. DNA damage induced the early activation of senescence markers, including an increase in the number of β-galactosidase-positive cells, the induction of p53 phosphorylation, and the increase in p16 and p19 protein. These changes were, however, not sufficient to reduce proliferation rates of PGC-1α-deficient MEFs at any cell passage tested. Moreover, PGC-1α-deficient cells escaped replicative senescence. Innovation & conclusion: PGC-1α plays an important role in the control of cellular senescence and immortalization.
eng
Immortalization
Mitochondria
Oxidative stress
PGC-1α
Senescence
Early induction of senescence and immortalization in PGC-1α-deficient mouse embryonic fibroblasts
research article
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
URL
https://repisalud.isciii.es/bitstreams/e0443229-4111-4bf7-85b3-3f26d7efdab1/download
File
MD5
d4eed9c37f9ab5f67d4eabc534f2f8dc
1989411
application/pdf
EarlyInductionOfSenescence_2019.pdf
URL
https://repisalud.isciii.es/bitstreams/257e3051-0c2a-4e84-9ba2-cb5c73b70ebb/download
File
MD5
d1d1e07e128e2e50873afb4317321337
508543
application/pdf
EarlyInductionOfSenescenceSupplementaryData1_2019.pdf
URL
https://repisalud.isciii.es/bitstreams/f8dbf584-c11a-4169-8f23-6628a11de2f3/download
File
MD5
d1d1e07e128e2e50873afb4317321337
508543
application/pdf
EarlyInductionOfSenescenceSupplementaryData1_2019.pdf
URL
https://repisalud.isciii.es/bitstreams/5fddc026-9b36-4968-869d-6ca6e0375947/download
File
MD5
06a1025543b4f58773e24eaf754f607a
251
text/plain
EarlyInductionOfSenescenceSupplementaryData3_2019.txt
URL
https://repisalud.isciii.es/bitstreams/2b18e0e1-e75a-4ae7-b91e-03827abd825e/download
File
MD5
8ccc85fed95f31a9ba4fd7bc9e794c5d
50051
text/plain
EarlyInductionOfSenescence_2019.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/4c2d1297-84ef-4d3b-ace8-f73dc506376b/download
File
MD5
1dbf5d5acf87bda41661a4157e24e8a8
1935
text/plain
EarlyInductionOfSenescenceSupplementaryData1_2019.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/b7a1ebf5-fb11-45bb-a7b8-8d4e5f9388f1/download
File
MD5
380f3f97e00c135dfb27085b6a7038aa
130
text/plain
EarlyInductionOfSenescenceSupplementaryData3_2019.txt.txt