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A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death
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(2011) A mitochondria-targeted inhibitor of cytochrome c peroxidase mitigates radiation-induced death. Nature Communications, 2 . Article: 497. doi:10.1038/ncomms1499 ISSN 2041-1723.
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Official URL: http://dx.doi.org/10.1038/ncomms1499
Abstract
The risk of radionuclide release in terrorist acts or exposure of healthy tissue during radiotherapy demand potent radioprotectants/radiomitigators. Ionizing radiation induces cell death by initiating the selective peroxidation of cardiolipin in mitochondria by the peroxidase activity of its complex with cytochrome c leading to release of haemoprotein into the cytosol and commitment to the apoptotic program. Here we design and synthesize mitochondria-targeted triphenylphosphonium-conjugated imidazole-substituted oleic and stearic acids that blocked peroxidase activity of cytochrome c/cardiolipin complex by specifically binding to its haem-iron. We show that both compounds inhibit pro-apoptotic oxidative events, suppress cyt c release, prevent cell death, and protect mice against lethal doses of irradiation. Significant radioprotective/radiomitigative effects of imidazole-substituted oleic acid are observed after pretreatment of mice from 1 h before through 24 h after the irradiation.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine |
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| Journal or Publication Title: | Nature Communications | ||||
| Publisher: | Nature Publishing Group | ||||
| ISSN: | 2041-1723 | ||||
| Official Date: | 11 October 2011 | ||||
| Dates: |
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| Volume: | 2 | ||||
| Page Range: | Article: 497 | ||||
| DOI: | 10.1038/ncomms1499 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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