Document Detail

Direct modification of the proinflammatory cytokine macrophage migration inhibitory factor by dietary isothiocyanates.
MedLine Citation:
PMID:  19776019     Owner:  NLM     Status:  MEDLINE    
Isothiocyanates are a class of phytochemicals with widely reported anti-cancer and anti-inflammatory activity. However, knowledge of their activity at a molecular level is limited. The objective of this study was to identify biological targets of phenethyl isothiocyanate (PEITC) using an affinity purification approach. An analogue of PEITC was synthesized to enable conjugation to a solid-phase resin. The pleiotropic cytokine macrophage migration inhibitory factor (MIF) was the major protein captured from cell lysates. Site-directed mutagenesis and mass spectrometry showed that PEITC covalently modified the N-terminal proline residue of MIF. This resulted in complete loss of catalytic tautomerase activity and disruption of protein conformation, as determined by impaired recognition by a monoclonal antibody directed to the region that receptors and interacting proteins bind to MIF. The conformational change was supported by in silico modeling. Monoclonal antibody binding to plasma MIF was disrupted in humans consuming watercress, a major dietary source of PEITC. The isothiocyanates have significant potential for development as MIF inhibitors, and this activity may contribute to the biological properties of these phytochemicals.
Kristin K Brown; Frances H Blaikie; Robin A J Smith; Joel D A Tyndall; Hongqi Lue; Jürgen Bernhagen; Christine C Winterbourn; Mark B Hampton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-23
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-16     Completed Date:  2009-12-14     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32425-33     Citation Subset:  IM    
Free Radical Research Group, Department of Pathology, University of Otago, Christchurch 8140, New Zealand.
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MeSH Terms
Amino Acid Sequence
Antibodies, Monoclonal / chemistry
Cell Membrane / metabolism
Cytokines / metabolism*
Dose-Response Relationship, Drug
Isothiocyanates / chemistry*
Jurkat Cells
Macrophage Migration-Inhibitory Factors / metabolism*
Models, Biological
Models, Chemical
Molecular Sequence Data
Mutagenesis, Site-Directed
Protein Conformation
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Cytokines; 0/Isothiocyanates; 0/Macrophage Migration-Inhibitory Factors

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

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