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Title

Early induction of senescence and immortalization in PGC-1α-deficient mouse embryonic fibroblasts

AuthorsPrieto, Ignacio; Zambrano, Alberto ; Laso, Javier; Aranda, Ana ; Samper, Enrique; Monsalve, María
Issue Date2018
Citation19th Biennial Meeting for the Society for Free Radical Research International (2018)
Abstract[Aims] Oxidative stress is known to induce early replicative senescence.Senescence has been proposed to work as a barrier to immortalizationand tumor development. Here, we aimed to evaluate the impact of theloss of peroxisome proliferator activated receptorγco-activator 1α(PGC-1α), a master regulator of oxidative metabolism and mitochondrial re-active oxygen species (ROS) generation, on replicative senescence andimmortalization in mouse embryonicfibroblasts (MEFs). [Results] We found that primary MEFs lacking PGC-1αshowed higher levelsof ROS than wild-type MEFs at all cell passages tested. The elevated pro-duction of ROS was associated with higher levels of oxidative DNA damageand the increased formation of DNA double-strand breaks. Evaluation ofthe induction of DNA repair systems in response toγ-radiation indicatedthat the loss of PGC-1αalso resulted in a small but significant reduction intheir activity. DNA damage induced the early activation of senescencemarkers, including an increase in the number ofβ-galactosidase-positivecells, the induction of p53 phosphorylation, and the increase in p16 and p19protein. These changes were, however, not sufficient to reduce proliferationrates of PGC-1α-deficient MEFs at any cell passage tested.
DescriptionResumen del póster presentado al 19th Biennial Meeting for the Society for Free Radical Research International (SFRRI), celebrado en Lisboa (Portugal) del 4 al 7 de junio de 2018.
URIhttp://hdl.handle.net/10261/190258
Appears in Collections:(IIBM) Comunicaciones congresos
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