Document Detail


Role of thiocyanate, bromide and hypobromous acid in hydrogen peroxide-induced apoptosis.
MedLine Citation:
PMID:  15104210     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously reported that H2O2-induced apoptosis in HL-60 human leukemia cells takes place in the presence of chloride, requires myeloperoxidase (MPO), and occurs through oxidative reactions involving hypochlorous acid and chloramines. We now report that when chloride is replaced by the pseudohalide thiocyanate, there is little or no H2O2-induced apoptosis. Furthermore, thiocyanate inhibits H2O2-induced apoptosis when chloride is present at physiological concentrations, and this occurs at thiocyanate concentrations that are present in human serum and saliva. In contrast, bromide can substitute for chloride in H2O2-induced apoptosis, but results in a lower percent of the cells induced into apoptosis. Hypobromous acid is likely a short-lived intermediate in this H2O2/MPO/bromide apoptosis, and reagent hypobromous acid and bromamines induce apoptosis in HL-60 cells. We conclude that the physiologic concentrations of thiocyanate found in human plasma could modulate the cytototoxicity of H2O2 and its resulting highly toxic MPO-generated hypochlorous acid by competing with chloride for MPO. Furthermore, the oxidative products of the reaction of thiocyanate with MPO are relatively innocuous for human leukemic cells in culture. In contrast, bromide can support H2O2/MPO/halide apoptosis, but is less potent than chloride and it has no effect in the presence of physiological levels of chloride.
Authors:
Brett A Wagner; Krzysztof J Reszka; Michael L McCormick; Bradley E Britigan; Crystal B Evig; C Patrick Burns
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Free radical research     Volume:  38     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-04-23     Completed Date:  2004-09-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  167-75     Citation Subset:  IM    
Affiliation:
Department of Medicine, Free Radical and Radiation Biology Graduate Program, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Amines / chemistry
Apoptosis* / drug effects
Bromates / toxicity*
Bromides / pharmacology*
Cell Survival
Chlorides / pharmacology
DNA Fragmentation
HL-60 Cells
Humans
Hydrogen Peroxide / antagonists & inhibitors,  toxicity*
Nitrobenzoates / metabolism
Oxidation-Reduction
Peroxidase / metabolism
Sulfhydryl Compounds
Taurine / analogs & derivatives*,  toxicity
Thiocyanates / pharmacology*
Grant Support
ID/Acronym/Agency:
P01CA66081/CA/NCI NIH HHS; R01 AI 34954/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Amines; 0/Bromates; 0/Bromides; 0/Chlorides; 0/Nitrobenzoates; 0/Sulfhydryl Compounds; 0/Thiocyanates; 107-35-7/Taurine; 13517-11-8/hypobromous acid; 15139-21-6/thionitrobenzoic acid; 302-04-5/thiocyanate; 52316-57-1/N-bromotaurine; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.7/Peroxidase

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


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