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- Mathew, Sherin TGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine (author)
Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation
- Article/chapterEnglish2014
Publisher, publication year, extent ...
- Elsevier BV,2014
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- LIBRIS-ID:oai:gup.ub.gu.se/198821
- https://gup.ub.gu.se/publication/198821URI
- https://doi.org/10.1016/j.taap.2014.02.013DOI
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- Language:English
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- Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2'-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. (c) 2014 Elsevier Inc. All rights reserved.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Biomedicinsk laboratorievetenskap/teknologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Medical Biotechnology Biomedical Laboratory Science/Technology hsv//eng
- Ionizing radiation
- Free radicals
- Nrf2
- Sulforaphane
- Cell survival
- DNA damage
- SMOKE-INDUCED EMPHYSEMA
- DOUBLE-STRAND BREAKS
- ANTIOXIDANT RESPONSE
- INDUCED APOPTOSIS
- OXIDATIVE STRESS
- GENE-EXPRESSION
- FREE-RADICALS
- DNA
- ENZYMES
- MICE
- ATES OF AMERICA
- V99
- P11908
- ATES OF AMERICA
- V98
- P3410
Added entries (persons, corporate bodies, meetings, titles ...)
- Bergström, PetraGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine(Swepub:gu)xbpeta (author)
- Hammarsten, OlaGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine(Swepub:gu)xhamol (author)
- Göteborgs universitetInstitutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin (creator_code:org_t)
Related titles
- In:Toxicology and Applied Pharmacology: Elsevier BV276:3, s. 188-1940041-008X
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