Academic Journal
Dexamethasone improves redox state in ataxia telangiectasia cells by promoting an NRF2-mediated antioxidant response
| العنوان: | Dexamethasone improves redox state in ataxia telangiectasia cells by promoting an NRF2-mediated antioxidant response |
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| المؤلفون: | Serena Brundu, Sara Biagiotti, Michele Menotta, Sara Orazi, Luciana Chessa, Luigia Rossi, Chiara Spapperi, Alessandra Fraternale, Mauro Magnani, Marzia Bianchi |
| سنة النشر: | 2016 |
| المجموعة: | Istituto Nazionale di Fisica Nucleare (INFN): Open Access Repository |
| مصطلحات موضوعية: | Cell Biology, Molecular Biology, Biochemistry |
| الوصف: | Ataxia telangiectasia (A-T) is a rare incurable neurodegenerative disease caused by biallelic mutations in the gene for ataxia-telangiectasia mutated (ATM). The lack of a functional ATM kinase leads to a pleiotropic phenotype, and oxidative stress is considered to have a crucial role in the complex physiopathology. Recently, steroids have been shown to reduce the neurological symptoms of the disease, although the molecular mechanism of this effect is largely unknown. In the present study, we have demonstrated that dexamethasone treatment of A-T lymphoblastoid cells increases the content of two of the most abundant antioxidants [glutathione (GSH) and NADPH] by up to 30%. Dexamethasone promoted the nuclear accumulation of the transcription factor nuclear factor (erythroid-derived 2)-like 2 to drive expression of antioxidant pathways involved in GSH synthesis and NADPH production. The latter effect was via glucose 6-phosphate dehydrogenase activation, as confirmed by increased enzyme activity and enhancement of the pentose phosphate pathway rate. This evidence indicates that glucocorticoids are able to potentiate antioxidant defenses to counteract oxidative stress in ataxia telangiectasia, and also reveals an unexpected role for dexamethasone in redox homeostasis and cellular antioxidant activity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | url:https://www.openaccessrepository.it/communities/itmirror; https://www.openaccessrepository.it/record/103741 |
| DOI: | 10.1111/febs.13901 |
| الاتاحة: | https://www.openaccessrepository.it/record/103741 https://doi.org/10.1111/febs.13901 |
| Rights: | info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.B0237B69 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/febs.13901 |
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