| Inactivation of tautomerase activity of macrophage migration inhibitory factor by sulforaphane: a potential biomarker for anti-inflammatory intervention. | |
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MedLine Citation:
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PMID: 21602309 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine with keto-enol tautomerase activity, rises rapidly in response to inflammation and is elevated in many chronic diseases. Isothiocyanates, such as sulforaphane from broccoli, are very potent inactivators of MIF tautomerase activity. A simple rapid method for determining this activity in tissues and body fluids may therefore be valuable for assessing severity of inflammation and efficacy of intervention. METHODS: Existing spectrophotometric assays of MIF, based on conversion of methyl L-dopachrome to methyl 5,6-dihydroxyindole-2-carboxylate and associated loss of absorption at 475 nm, lack sensitivity. Assay sensitivity and efficiency were markedly improved by reducing the nonenzymatic rate, by lowering pH to 6.2, replacing phosphate (which catalyzes the reaction) with Bis-Tris buffer, and converting to a microtiter plate format. RESULTS: A structure-potency study of MIF tautomerase inactivation by isothiocyanates showed that sulforaphane, benzyl, n-hexyl, and phenethyl isothiocyanates were especially potent. MIF tautomerase could be readily quantified in human urine concentrated by ultrafiltration. This activity comprised: (i) a heat-labile, sulforaphane-inactivated macromolecular fraction (presumably MIF) that was concentrated during ultrafiltration; (ii) a flow-through fraction, with constant activity during filtration, that was heat stable and insensitive to sulforaphane. Administration of the sulforaphane precursor glucoraphanin to human volunteers almost completely abolished urinary tautomerase activity, which recovered over many hours. CONCLUSION: A simple, rapid, quantitative MIF tautomerase assay has been developed as a potential biomarker for assessing inflammatory severity and effectiveness of intervention. IMPACT: An improved assay for measuring MIF tautomerase activity and its applications are described. |
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Authors:
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Zachary R Healy; Hua Liu; W David Holtzclaw; Paul Talalay |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-05-20 |
Journal Detail:
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Title: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Volume: 20 ISSN: 1538-7755 ISO Abbreviation: Cancer Epidemiol. Biomarkers Prev. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-07-08 Completed Date: 2011-11-09 Revised Date: 2013-05-24 |
Medline Journal Info:
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Nlm Unique ID: 9200608 Medline TA: Cancer Epidemiol Biomarkers Prev Country: United States |
Other Details:
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Languages: eng Pagination: 1516-23 Citation Subset: IM |
Copyright Information:
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©2011 AACR |
Affiliation:
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The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Markers / metabolism Enzyme Inhibitors / metabolism, pharmacology Humans Inflammation / metabolism* Intramolecular Oxidoreductases / antagonists & inhibitors* Isothiocyanates / metabolism, pharmacology Macrophage Migration-Inhibitory Factors / analysis, chemistry, metabolism* Mice Sensitivity and Specificity Spectrophotometry / methods Thiocyanates / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA093780-08/CA/NCI NIH HHS; R01 CA094076-10/CA/NCI NIH HHS; R01CA93780/CA/NCI NIH HHS; R01CA94076/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Enzyme Inhibitors; 0/Isothiocyanates; 0/Macrophage Migration-Inhibitory Factors; 0/Thiocyanates; 4478-93-7/sulforafan; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.2.1/phenylpyruvate tautomerase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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