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Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells
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 dysfu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156351/ https://www.ncbi.nlm.nih.gov/pubmed/30028071 http://dx.doi.org/10.1111/acel.12812 |
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author | Zamponi, Emiliano Zamponi, Nahuel Coskun, Pinar Quassollo, Gonzalo Lorenzo, Alfredo Cannas, Sergio A. Pigino, Gustavo Chialvo, Dante R. Gardiner, Katheleen Busciglio, Jorge Helguera, Pablo |
author_facet | Zamponi, Emiliano Zamponi, Nahuel Coskun, Pinar Quassollo, Gonzalo Lorenzo, Alfredo Cannas, Sergio A. Pigino, Gustavo Chialvo, Dante R. Gardiner, Katheleen Busciglio, Jorge Helguera, Pablo |
author_sort | Zamponi, Emiliano |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6156351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61563512018-10-01 Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells Zamponi, Emiliano Zamponi, Nahuel Coskun, Pinar Quassollo, Gonzalo Lorenzo, Alfredo Cannas, Sergio A. Pigino, Gustavo Chialvo, Dante R. Gardiner, Katheleen Busciglio, Jorge Helguera, Pablo Aging Cell Original Paper 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. John Wiley and Sons Inc. 2018-07-20 2018-10 /pmc/articles/PMC6156351/ /pubmed/30028071 http://dx.doi.org/10.1111/acel.12812 Text en © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Paper Zamponi, Emiliano Zamponi, Nahuel Coskun, Pinar Quassollo, Gonzalo Lorenzo, Alfredo Cannas, Sergio A. Pigino, Gustavo Chialvo, Dante R. Gardiner, Katheleen Busciglio, Jorge Helguera, Pablo Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells |
title | Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells |
title_full | Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells |
title_fullStr | Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells |
title_full_unstemmed | Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells |
title_short | Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells |
title_sort | nrf2 stabilization prevents critical oxidative damage in down syndrome cells |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156351/ https://www.ncbi.nlm.nih.gov/pubmed/30028071 http://dx.doi.org/10.1111/acel.12812 |
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