Document Detail


Mitochondria-targeted (2-hydroxyamino-vinyl)-triphenyl-phosphonium releases NO(.) and protects mouse embryonic cells against irradiation-induced apoptosis.
MedLine Citation:
PMID:  19427865     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Natalia A Belikova; Jianfei Jiang; Detcho A Stoyanovsky; Ashley Glumac; Hülya Bayir; Joel S Greenberger; Valerian E Kagan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-05-08
Journal Detail:
Title:  FEBS letters     Volume:  583     ISSN:  1873-3468     ISO Abbreviation:  FEBS Lett.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-15     Completed Date:  2009-07-02     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1945-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
HL-70755/HL/NHLBI NIH HHS; R01 HL070755/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:
0/(2-hydroxyaminovinyl)triphenylphosphonium; 0/Hydroxylamines; 0/Nitric Oxide Donors; 0/Organophosphorus Compounds; 0/Radiation-Protective Agents; 31C4KY9ESH/Nitric Oxide
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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