{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:53:17Z","timestamp":1784375597235,"version":"3.55.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2012,4,17]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>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. Macrophage migration inhibitory factor has been shown to mediate both disease-exacerbating and beneficial effects, but the underlying mechanism(s) controlling these diverse functions are poorly understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Here, we have identified an\n              <jats:italic>S<\/jats:italic>\n              -nitros(yl)ation modification of MIF that regulates the protective functional phenotype of MIF in myocardial reperfusion injury. Macrophage migration inhibitory factor contains 3 cysteine (Cys) residues; using recombinant wtMIF and site-specific MIF mutants, we have identified that Cys-81 is modified by\n              <jats:italic>S<\/jats:italic>\n              -nitros(yl)ation whereas the CXXC-derived Cys residues of MIF remained unaffected. The selective\n              <jats:italic>S<\/jats:italic>\n              -nitrosothiol formation at Cys-81 led to a doubling of the oxidoreductase activity of MIF. Importantly,\n              <jats:italic>S<\/jats:italic>\n              -nitrosothiol-MIF formation was measured both in vitro and in vivo and led to a decrease in cardiomyocyte apoptosis in the reperfused heart. This decrease was paralleled by a\n              <jats:italic>S<\/jats:italic>\n              -nitrosothiol-MIF\u2013 but not Cys81 serine (Ser)\u2013MIF mutant\u2013dependent reduction of infarct size in an in vivo model of myocardial ischemia\/reperfusion injury.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              <jats:italic>S<\/jats:italic>\n              -nitros(yl)ation of MIF is a pivotal novel regulatory mechanism, providing enhanced activity resulting in increased cytoprotection in myocardial reperfusion injury.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.111.069104","type":"journal-article","created":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T04:26:05Z","timestamp":1331699165000},"page":"1880-1889","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":85,"title":["Cardioprotection Through\n            <i>S<\/i>\n            -Nitros(yl)ation of Macrophage Migration Inhibitory Factor"],"prefix":"10.1161","volume":"125","author":[{"given":"Peter","family":"Luedike","sequence":"first","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike B.","family":"Hendgen-Cotta","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Sobierajski","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Totzeck","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Reeh","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Dewor","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqi","family":"Lue","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Krisp","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Wolters","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[{"name":"From the University Hospital D\u00fcsseldorf, Medical Faculty, Division of Cardiology, Pulmonology, and Vascular Medicine, D\u00fcsseldorf (P.L., U.B.H.-C., J.S., M.T., M.R., M.K.T.R.); RWTH Aachen University, Institute of Biochemistry and Molecular Cell Biology, Aachen (P.L., M.R., M.D., H.L., J.B.); Ruhr-University Bochum, Department of Analytical Chemistry, Bochum (C.K., D.W.); all of 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