Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila.

Détails

ID Serval
serval:BIB_020206E49E0C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila.
Périodique
Developmental Cell
Auteur⸱e⸱s
Sykiotis G.P., Bohmann D.
ISSN
1534-5807 (Print)
ISSN-L
1534-5807
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
14
Numéro
1
Pages
76-85
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Keap1/Nrf2 signaling defends organisms against the detrimental effects of oxidative stress and has been suggested to abate its consequences, including aging-associated diseases like neurodegeneration, chronic inflammation, and cancer. Nrf2 is a prominent target for drug discovery, and Nrf2-activating agents are in clinical trials for cancer chemoprevention. However, aberrant activation of Nrf2 by keap1 somatic mutations may contribute to carcinogenesis and promote resistance to chemotherapy. To evaluate potential functions of Keap1 and Nrf2 for organismal homeostasis, we characterized the pathway in Drosophila. We demonstrate that Keap1/Nrf2 signaling in the fruit fly is activated by oxidants, induces antioxidant and detoxification responses, and confers increased tolerance to oxidative stress. Importantly, keap1 loss-of-function mutations extend the lifespan of Drosophila males, supporting a role for Nrf2 signaling in the regulation of longevity. Interestingly, cancer chemopreventive drugs potently stimulate Drosophila Nrf2 activity, suggesting the fruit fly as an experimental system to identify and characterize such agents.
Mots-clé
Aging/physiology, Animals, Cell Survival/drug effects, Conserved Sequence, Drosophila/genetics, Drosophila/growth & development, Drosophila Proteins/genetics, Drosophila Proteins/physiology, Female, Gene Expression Regulation, Intracellular Signaling Peptides and Proteins/genetics, Intracellular Signaling Peptides and Proteins/physiology, Life Expectancy, Male, Mutation, NF-E2-Related Factor 2/genetics, NF-E2-Related Factor 2/physiology, Oxidative Stress, Paraquat/toxicity, Signal Transduction, Transcriptional Activation
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/01/2015 13:46
Dernière modification de la notice
20/08/2019 12:24
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