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Glutathione maintenance mitigates age-related susceptibility to redox cycling agents

التفاصيل البيبلوغرافية
العنوان: Glutathione maintenance mitigates age-related susceptibility to redox cycling agents
المؤلفون: Nicholas O. Thomas, Kate P. Shay, Amanda R. Kelley, Judy A. Butler, Tory M. Hagen
المصدر: Redox Biology, Vol 10, Iss C, Pp 45-52 (2016)
بيانات النشر: Elsevier, 2016.
سنة النشر: 2016
المجموعة: LCC:Medicine (General)
LCC:Biology (General)
مصطلحات موضوعية: BSO (PubChem CID: 119565), DMF (PubChem CID: 6228), NAC (PubChem CID: 12035), Menadione (PubChem CID: 4055), Medicine (General), R5-920, Biology (General), QH301-705.5
الوصف: Isolated hepatocytes from young (4–6 mo) and old (24–26 mo) F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC50 for young: 405 μM; LC50 for old: 275 μM). Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(P)H: quinone oxido-reductase 1 (NQO1) protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0.0019 and p=0.018; N=3), but glutathione peroxidase 4 (GPX4) declined by 70% (p=0.0043; N=3). These results indicate toxicity may stem from vulnerability to lipid peroxidation instead of inadequate reduction of menadione semi-quinone. Lipid peroxidation was 2-fold higher, and GSH declined by a 3-fold greater margin in old versus young rat cells given 300 µM menadione (p2-fold reduction in cell death, suggesting that the age-related increase in menadione susceptibility likely stems from attenuated GSH-dependent defenses. This data identifies cellular targets for intervention in order to limit age-related toxicological insults to menadione and potentially other redox cycling compounds.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2213-2317
Relation: http://www.sciencedirect.com/science/article/pii/S2213231716301434; https://doaj.org/toc/2213-2317
DOI: 10.1016/j.redox.2016.09.010
URL الوصول: https://doaj.org/article/2f5209aa31f54db09bfe21315c30cd0e
رقم الأكسشن: edsdoj.2f5209aa31f54db09bfe21315c30cd0e
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:22132317
DOI:10.1016/j.redox.2016.09.010