|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2001-2-8
|
|
pubmed:abstractText |
Although the pseudohalide thiocyanate (SCN(-)) is the preferred substrate for eosinophil peroxidase (EPO) in fluids of physiologic halide composition, the product(s) of this reaction have not been directly identified, and mechanisms underlying their cytotoxic potential are poorly characterized. We used nuclear magnetic resonance spectroscopy (NMR), electrospray ionization mass spectrometry, and quantitative chemical analysis to identify the principal reaction products of both the EPO/SCN(-)/H(2)O(2) system and activated eosinophils as roughly equimolar amounts of OSCN(-) (hypothiocyanite) and OCN(-) (cyanate). Red blood cells exposed to increasing concentrations of OSCN(-)/OCN(-) are first depleted of glutathione, after which glutathione S-transferase and glyceraldehyde-3-phosphate dehydrogenase then ATPases undergo sulfhydryl (SH) reductant-reversible inactivation before lysing. OSCN(-)/OCN(-) inactivates red blood cell membrane ATPases 10-1000 times more potently than do HOCl, HOBr, and H(2)O(2). Exposure of glutathione S-transferase to [(14)C]OSCN(-)/OCN(-) causes SH reductant-reversible disulfide bonding and covalent isotope labeling. We propose that EPO/SCN(-)/H(2)O(2) reaction products comprise a potential SH-targeted cytotoxic system that functions in striking contrast to HOCl, the highly but relatively indiscriminantly reactive product of the neutrophil myeloperoxidase system.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyanates,
http://linkedlifedata.com/resource/pubmed/chemical/Eosinophil Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidases,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Thiocyanates,
http://linkedlifedata.com/resource/pubmed/chemical/hypothiocyanite ion,
http://linkedlifedata.com/resource/pubmed/chemical/thiocyanate
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jan
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
5
|
|
pubmed:volume |
276
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
215-24
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:11013238-Adenosine Triphosphatases,
pubmed-meshheading:11013238-Cyanates,
pubmed-meshheading:11013238-Eosinophil Peroxidase,
pubmed-meshheading:11013238-Eosinophils,
pubmed-meshheading:11013238-Erythrocytes,
pubmed-meshheading:11013238-Glutathione,
pubmed-meshheading:11013238-Glutathione Transferase,
pubmed-meshheading:11013238-Hemolysis,
pubmed-meshheading:11013238-Humans,
pubmed-meshheading:11013238-Hydrogen Peroxide,
pubmed-meshheading:11013238-Hydrogen-Ion Concentration,
pubmed-meshheading:11013238-Kinetics,
pubmed-meshheading:11013238-Magnetic Resonance Spectroscopy,
pubmed-meshheading:11013238-Neutrophils,
pubmed-meshheading:11013238-Oxidants,
pubmed-meshheading:11013238-Peroxidase,
pubmed-meshheading:11013238-Peroxidases,
pubmed-meshheading:11013238-Spectrometry, Mass, Electrospray Ionization,
pubmed-meshheading:11013238-Temperature,
pubmed-meshheading:11013238-Tetradecanoylphorbol Acetate,
pubmed-meshheading:11013238-Thiocyanates
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Eosinophil peroxidase oxidation of thiocyanate. Characterization of major reaction products and a potential sulfhydryl-targeted cytotoxicity system.
|
|
pubmed:affiliation |
Department of Internal Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
