| Mitochondria-targeted (2-hydroxyamino-vinyl)-triphenyl-phosphonium releases NO(.) and protects mouse embryonic cells against irradiation-induced apoptosis. | |
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MedLine Citation:
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PMID: 19427865 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Generation of reactive oxygen species by damaged respiratory chain followed by the formation of cytochrome c (cyt c)-cardiolipin (CL) complex with peroxidase activity are early events in apoptosis. By quenching the peroxidase activity of cyt c-CL complexes in mitochondria, nitric oxide can exert anti-apoptotic effects. Therefore, mitochondria-targeted pro-drugs capable of gradual nitric oxide radical (NO*) release are promising radioprotectants. Here we demonstrate that (2-hydroxyamino-vinyl)-triphenyl-phosphonium effectively accumulates in mitochondria, releases NO* upon mitochondrial peroxidase reaction, protects mouse embryonic cells from irradiation-induced apoptosis and increases their clonogenic survival after irradiation. We conclude that mitochondria-targeted peroxidase-activatable NO-donors represent a new interesting class of radioprotectors. |
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Authors:
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Natalia A Belikova; Jianfei Jiang; Detcho A Stoyanovsky; Ashley Glumac; Hülya Bayir; Joel S Greenberger; Valerian E Kagan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-05-08 |
Journal Detail:
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Title: FEBS letters Volume: 583 ISSN: 1873-3468 ISO Abbreviation: FEBS Lett. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-15 Completed Date: 2009-07-02 Revised Date: 2013-06-02 |
Medline Journal Info:
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Nlm Unique ID: 0155157 Medline TA: FEBS Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1945-50 Citation Subset: IM |
Affiliation:
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Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15219, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects*, physiology*, radiation effects Biotransformation Cell Survival / drug effects, physiology, radiation effects Cells, Cultured Colony-Forming Units Assay Gamma Rays Hydroxylamines / pharmacokinetics, pharmacology* Membrane Potential, Mitochondrial Mice Mitochondria / drug effects, metabolism Nitric Oxide / metabolism* Nitric Oxide Donors / pharmacokinetics, pharmacology Organophosphorus Compounds / pharmacokinetics, pharmacology* Radiation-Protective Agents / pharmacokinetics, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL-70755/HL/NHLBI NIH HHS; R01 HL070755-05/HL/NHLBI NIH HHS; R01 HL070755-06/HL/NHLBI NIH HHS; U19 AI068021-030002/AI/NIAID NIH HHS; U19 AI068021-040002/AI/NIAID NIH HHS; U19-AI068021/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/(2-hydroxyaminovinyl)triphenylphosphonium; 0/Hydroxylamines; 0/Nitric Oxide Donors; 0/Organophosphorus Compounds; 0/Radiation-Protective Agents; 10102-43-9/Nitric Oxide |
| Comments/Corrections | |
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