Document Detail

Cardioprotection Through S-Nitros(yl)ation of MacrophageMigration Inhibitory Factor.
MedLine Citation:
PMID:  22415145     Owner:  NLM     Status:  Publisher    
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a structurally unique inflammatory cytokine that controls cellular signaling in human physiology and disease through extra- and intracellular processes. MIF has been shown to mediate both disease-exacerbating and beneficial effects, but the underlying mechanism(s) controlling these diverse functions are poorly understood. METHODS AND RESULTS: Here, we have identified an S-nitros(yl)ation modification of MIF which regulates the protective functional phenotype of MIF in myocardial reperfusion injury. MIF contains three cysteine (Cys) residues; using recombinant wtMIF and site-specific MIF mutants, we have identified Cys-81 to be modified by S-nitros(yl)ation, whereas the CXXC-derived Cys residues of MIF remained unaffected. The selective S-nitrosothiol (SNO) formation at Cys-81 led to a doubling of the oxidoreductase activity of MIF. Importantly, SNO-MIF formation was measured both in vitro and in vivo and led to a decrease in cardiomyocyte apoptosis in the reperfused heart. This was paralleled by a SNO-MIF- but not Cys81Ser-MIF mutant-dependent reduction of infarct size in an in vivo model of myocardial ischemia/reperfusion (I/R) injury. CONCLUSIONS: S-nitros(yl)ation of MIF is a pivotal novel regulatory mechanism, providing enhanced activity resulting in increased cytoprotection in myocardial reperfusion injury.
Peter Lüdike; Ulrike B Hendgen-Cotta; Julia Sobierajski; Matthias Totzeck; Marcel Reeh; Manfred Dewor; Hongqi Lue; Christoph Krisp; Dirk Wolters; Malte Kelm; Jürgen Bernhagen; Tienush Rassaf
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-13
Journal Detail:
Title:  Circulation     Volume:  -     ISSN:  1524-4539     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1 University Hospital Düsseldorf, Düsseldorf & RWTH Aachen University, Aachen, Germany;
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