Artículo
Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells
Zamponi, Emiliano
; Zamponi, Nahuel
; Coskun, Pinar; Quassollo Infanzon, Gonzalo Emiliano
; Lorenzo, Alfredo Guillermo
; Cannas, Sergio Alejandro
; Pigino, Gustavo Fernando
; Chialvo, Dante Renato
; Gardiner, Katheleen; Busciglio, Jorge; Helguera, Pablo Rodolfo
Fecha de publicación:
10/2018
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
Aging Cell
ISSN:
1474-9718
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Mounting evidence implicates chronic oxidative stress as a critical driver of the aging process. Down syndrome (DS) is characterized by a complex phenotype, including early senescence. DS cells display increased levels of reactive oxygen species (ROS) and mitochondrial structural and metabolic dysfunction, which are counterbalanced by sustained Nrf2-mediated transcription of cellular antioxidant response elements (ARE). Here, we show that caspase 3/PKCδdependent activation of the Nrf2 pathway in DS and Dp16 (a mouse model of DS) cells is necessary to protect against chronic oxidative damage and to preserve cellular functionality. Mitochondria-targeted catalase (mCAT) significantly reduced oxidative stress, restored mitochondrial structure and function, normalized replicative and wound healing capacity, and rendered the Nrf2-mediated antioxidant response dispensable. These results highlight the critical role of Nrf2/ARE in the maintenance of DS cell homeostasis and validate mitochondrial-specific interventions as a key aspect of antioxidant and antiaging therapies.
Palabras clave:
DOWN SYNDROME
,
DP16
,
MITOCHONDRIAL CATALASE
,
NRF2
,
OXIDATIVE STRESS
,
PKC-Delta
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Articulos(IFEG)
Articulos de INST.DE FISICA ENRIQUE GAVIOLA
Articulos de INST.DE FISICA ENRIQUE GAVIOLA
Articulos(INIMEC - CONICET)
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Articulos de INSTITUTO DE INV. MEDICAS MERCEDES Y MARTIN FERREYRA
Citación
Zamponi, Emiliano; Zamponi, Nahuel; Coskun, Pinar; Quassollo Infanzon, Gonzalo Emiliano; Lorenzo, Alfredo Guillermo; et al.; Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells; Wiley Blackwell Publishing, Inc; Aging Cell; 17; 5; 10-2018; 1-22
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