Nrf2 Stabilization Prevents Critical Oxidative Damage in Down Syndrome Cells

Overview

Journal Aging Cell

Specialties Cell Biology
Geriatrics

Date 2018 Jul 21

PMID 30028071

Citations 29

Authors

Emiliano Zamponi

Nahuel Zamponi

Pinar Coskun

Gonzalo Quassollo

Alfredo Lorenzo

Sergio A Cannas

Gustavo Pigino

Dante R Chialvo

Katheleen Gardiner

Jorge Busciglio

Pablo Helguera

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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