Document Detail


Inactivation of thiol-dependent enzymes by hypothiocyanous acid: role of sulfenyl thiocyanate and sulfenic acid intermediates.
MedLine Citation:
PMID:  22248862     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Myeloperoxidase (MPO) forms reactive oxidants including hypochlorous and hypothiocyanous acids (HOCl and HOSCN) under inflammatory conditions. HOCl causes extensive tissue damage and plays a role in the progression of many inflammatory-based diseases. Although HOSCN is a major MPO oxidant, particularly in smokers, who have elevated plasma thiocyanate, the role of this oxidant in disease is poorly characterized. HOSCN induces cellular damage by targeting thiols. However, the specific targets and mechanisms involved in this process are not well defined. We show that exposure of macrophages to HOSCN results in the inactivation of intracellular enzymes, including creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In each case, the active-site thiol residue is particularly sensitive to oxidation, with evidence for reversible inactivation and the formation of sulfenyl thiocyanate and sulfenic acid intermediates, on treatment with HOSCN (less than fivefold molar excess). Experiments with DAz-2, a cell-permeable chemical trap for sulfenic acids, demonstrate that these intermediates are formed on many cellular proteins, including GAPDH and CK, in macrophages exposed to HOSCN. This is the first direct evidence for the formation of protein sulfenic acids in HOSCN-treated cells and highlights the potential of this oxidant to perturb redox signaling processes.
Authors:
Tessa J Barrett; David I Pattison; Stephen E Leonard; Kate S Carroll; Michael J Davies; Clare L Hawkins
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-08
Journal Detail:
Title:  Free radical biology & medicine     Volume:  52     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-06-25     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1075-85     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
The Heart Research Institute, Newtown, NSW 2042, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Catalytic Domain
Cell Line
Creatine Kinase / chemistry,  metabolism
Enzyme Activation / drug effects
Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / chemistry,  metabolism
Macrophages / drug effects,  enzymology*
Mice
Oxidative Stress
Peroxidase / metabolism*
Sulfenic Acids / chemistry,  pharmacology*
Sulfhydryl Compounds / chemistry
Thiocyanates / chemistry,  pharmacology*
Grant Support
ID/Acronym/Agency:
R01 GM102187/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Sulfenic Acids; 0/Sulfhydryl Compounds; 0/Thiocyanates; 0/hypothiocyanous acid; EC 1.11.1.7/Peroxidase; EC 1.2.1.9/Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); EC 2.7.3.2/Creatine Kinase
Comments/Corrections

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