Targeted intracellular accumulation of macrophage migration inhibitory factor in the reperfused heart mediates cardioprotection
Summary S -nitrosation of macrophage migration inhibitory factor (MIF) has been shown to be cytoprotective in myocardial ischaemia/reperfusion (I/R) injury. Since the exact mechanism of action is unknown, we here characterise the cardioprotective effects of targeted intracellular accumulation of MIF...
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| Veröffentlicht in: | Thrombosis and haemostasis 2016-01, Vol.115 (1), p.200-212 |
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| creator | Pohl, Julia Hendgen-Cotta, Ulrike R. Rammos, Christos Luedike, Peter Mull, Elena Stoppe, Christian Jülicher, Karen Lue, Hongqi Merx, Marc Kelm, Malte Bernhagen, Jürgen Rassaf, Tienush |
| description | Summary
S
-nitrosation of macrophage migration inhibitory factor (MIF) has been shown to be cytoprotective in myocardial ischaemia/reperfusion (I/R) injury. Since the exact mechanism of action is unknown, we here characterise the cardioprotective effects of targeted intracellular accumulation of MIF in myocardial I/R injury. We used different
in vivo
,
ex vivo
and
in vitro
models of myocardial I/R and hypoxia/reoxyge-nation (H/R) injury to determine MIF levels by immunoblots and ELISA in different phases of reperfusion and reoxygenation, respectively. We discovered a rapid decrease of cardiac MIF that was specific to the early phase of reperfusion. Posttranslational modification of MIF via
S
-nitrosation – proofed by a modified version of the Biotin Switch Assay – prevented this rapid decrease, leading to a targeted intracellular accumulation of MIF in the early phase of reperfusion. Intracellular MIF accumulation preserved the intracellular ability of MIF to reduce oxidative stress as shown by hydrogen peroxide and aconitase activity measurements. Infarct size measurements by TTC staining showed an overall enhanced cardioprotective effect of this protein by reduction of reperfusion injury. In summary, we have unravelled a novel mechanism of MIF-mediated cardioprotection. Targeted intra-cellular accumulation of MIF by
S
-nitrosation may offer a novel therapeutic approach in the treatment of myocardial I/R-injury. |
| doi_str_mv | 10.1160/TH15-05-0436 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1160_TH15_05_0436</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>26310191</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-9351bc4df795fc82770dc31902a8b406363217ec3f6007b29e3d2447a2fac90e3</originalsourceid><addsrcrecordid>eNptkM1LxDAQxYMo7rp68yy5azVfTTZHWfyCBS8reCtpOtlmabclTQ978l83S9WTMDDD8OPx3kPompJ7SiV52LzSPCNpBJcnaM5yqTK51J-naE64IJlkIp-hi2HYEUKl0Pk5mjHJKaGaztHXxoQtRKiw38dgLDTN2JiAjbVjm67ouz3uHG6NDV1fmy3g1m_D9Pf72pc-duGAnbFppw-ONeAAPQQ3Dkm2BhMibqHyJsKArQmV7_rQRbBHjUt05kwzwNXPXqCP56fN6jVbv7-8rR7XmRVKxEzznJZWVE7p3NklU4pUllNNmFmWgkguOaMKLHeSEFUyDbxiQijDkjFNgC_Q3aSbYgxDAFf0wbcmHApKimOPxbHHgqRJPSb8ZsL7sUze_-Df4hJwOwGx9tBCsevGsE8B_pf7BpKufow</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Targeted intracellular accumulation of macrophage migration inhibitory factor in the reperfused heart mediates cardioprotection</title><source>MEDLINE</source><source>Thieme Connect Journals</source><creator>Pohl, Julia ; Hendgen-Cotta, Ulrike R. ; Rammos, Christos ; Luedike, Peter ; Mull, Elena ; Stoppe, Christian ; Jülicher, Karen ; Lue, Hongqi ; Merx, Marc ; Kelm, Malte ; Bernhagen, Jürgen ; Rassaf, Tienush</creator><creatorcontrib>Pohl, Julia ; Hendgen-Cotta, Ulrike R. ; Rammos, Christos ; Luedike, Peter ; Mull, Elena ; Stoppe, Christian ; Jülicher, Karen ; Lue, Hongqi ; Merx, Marc ; Kelm, Malte ; Bernhagen, Jürgen ; Rassaf, Tienush</creatorcontrib><description>Summary
S
-nitrosation of macrophage migration inhibitory factor (MIF) has been shown to be cytoprotective in myocardial ischaemia/reperfusion (I/R) injury. Since the exact mechanism of action is unknown, we here characterise the cardioprotective effects of targeted intracellular accumulation of MIF in myocardial I/R injury. We used different
in vivo
,
ex vivo
and
in vitro
models of myocardial I/R and hypoxia/reoxyge-nation (H/R) injury to determine MIF levels by immunoblots and ELISA in different phases of reperfusion and reoxygenation, respectively. We discovered a rapid decrease of cardiac MIF that was specific to the early phase of reperfusion. Posttranslational modification of MIF via
S
-nitrosation – proofed by a modified version of the Biotin Switch Assay – prevented this rapid decrease, leading to a targeted intracellular accumulation of MIF in the early phase of reperfusion. Intracellular MIF accumulation preserved the intracellular ability of MIF to reduce oxidative stress as shown by hydrogen peroxide and aconitase activity measurements. Infarct size measurements by TTC staining showed an overall enhanced cardioprotective effect of this protein by reduction of reperfusion injury. In summary, we have unravelled a novel mechanism of MIF-mediated cardioprotection. Targeted intra-cellular accumulation of MIF by
S
-nitrosation may offer a novel therapeutic approach in the treatment of myocardial I/R-injury.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1160/TH15-05-0436</identifier><identifier>PMID: 26310191</identifier><language>eng</language><publisher>Schattauer: Schattauer GmbH</publisher><subject>Aconitate Hydratase - metabolism ; Animals ; Atherosclerosis and Ischaemic Disease ; Cell Line ; Disease Models, Animal ; Hydrogen Peroxide - metabolism ; Intramolecular Oxidoreductases - deficiency ; Intramolecular Oxidoreductases - genetics ; Intramolecular Oxidoreductases - metabolism ; Macrophage Migration-Inhibitory Factors - deficiency ; Macrophage Migration-Inhibitory Factors - genetics ; Macrophage Migration-Inhibitory Factors - metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardial Infarction - genetics ; Myocardial Infarction - metabolism ; Myocardial Infarction - pathology ; Myocardial Infarction - prevention & control ; Myocardial Reperfusion Injury - genetics ; Myocardial Reperfusion Injury - metabolism ; Myocardial Reperfusion Injury - pathology ; Myocardial Reperfusion Injury - prevention & control ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Nitrosation ; Oxidative Stress ; Protein Processing, Post-Translational ; Time Factors</subject><ispartof>Thrombosis and haemostasis, 2016-01, Vol.115 (1), p.200-212</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-9351bc4df795fc82770dc31902a8b406363217ec3f6007b29e3d2447a2fac90e3</citedby><cites>FETCH-LOGICAL-c474t-9351bc4df795fc82770dc31902a8b406363217ec3f6007b29e3d2447a2fac90e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1160/TH15-05-0436.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1160/TH15-05-0436$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,776,780,3005,27901,27902,54534,54535</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26310191$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pohl, Julia</creatorcontrib><creatorcontrib>Hendgen-Cotta, Ulrike R.</creatorcontrib><creatorcontrib>Rammos, Christos</creatorcontrib><creatorcontrib>Luedike, Peter</creatorcontrib><creatorcontrib>Mull, Elena</creatorcontrib><creatorcontrib>Stoppe, Christian</creatorcontrib><creatorcontrib>Jülicher, Karen</creatorcontrib><creatorcontrib>Lue, Hongqi</creatorcontrib><creatorcontrib>Merx, Marc</creatorcontrib><creatorcontrib>Kelm, Malte</creatorcontrib><creatorcontrib>Bernhagen, Jürgen</creatorcontrib><creatorcontrib>Rassaf, Tienush</creatorcontrib><title>Targeted intracellular accumulation of macrophage migration inhibitory factor in the reperfused heart mediates cardioprotection</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
S
-nitrosation of macrophage migration inhibitory factor (MIF) has been shown to be cytoprotective in myocardial ischaemia/reperfusion (I/R) injury. Since the exact mechanism of action is unknown, we here characterise the cardioprotective effects of targeted intracellular accumulation of MIF in myocardial I/R injury. We used different
in vivo
,
ex vivo
and
in vitro
models of myocardial I/R and hypoxia/reoxyge-nation (H/R) injury to determine MIF levels by immunoblots and ELISA in different phases of reperfusion and reoxygenation, respectively. We discovered a rapid decrease of cardiac MIF that was specific to the early phase of reperfusion. Posttranslational modification of MIF via
S
-nitrosation – proofed by a modified version of the Biotin Switch Assay – prevented this rapid decrease, leading to a targeted intracellular accumulation of MIF in the early phase of reperfusion. Intracellular MIF accumulation preserved the intracellular ability of MIF to reduce oxidative stress as shown by hydrogen peroxide and aconitase activity measurements. Infarct size measurements by TTC staining showed an overall enhanced cardioprotective effect of this protein by reduction of reperfusion injury. In summary, we have unravelled a novel mechanism of MIF-mediated cardioprotection. Targeted intra-cellular accumulation of MIF by
S
-nitrosation may offer a novel therapeutic approach in the treatment of myocardial I/R-injury.</description><subject>Aconitate Hydratase - metabolism</subject><subject>Animals</subject><subject>Atherosclerosis and Ischaemic Disease</subject><subject>Cell Line</subject><subject>Disease Models, Animal</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Intramolecular Oxidoreductases - deficiency</subject><subject>Intramolecular Oxidoreductases - genetics</subject><subject>Intramolecular Oxidoreductases - metabolism</subject><subject>Macrophage Migration-Inhibitory Factors - deficiency</subject><subject>Macrophage Migration-Inhibitory Factors - genetics</subject><subject>Macrophage Migration-Inhibitory Factors - metabolism</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myocardial Infarction - genetics</subject><subject>Myocardial Infarction - metabolism</subject><subject>Myocardial Infarction - pathology</subject><subject>Myocardial Infarction - prevention & control</subject><subject>Myocardial Reperfusion Injury - genetics</subject><subject>Myocardial Reperfusion Injury - metabolism</subject><subject>Myocardial Reperfusion Injury - pathology</subject><subject>Myocardial Reperfusion Injury - prevention & control</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Nitrosation</subject><subject>Oxidative Stress</subject><subject>Protein Processing, Post-Translational</subject><subject>Time Factors</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkM1LxDAQxYMo7rp68yy5azVfTTZHWfyCBS8reCtpOtlmabclTQ978l83S9WTMDDD8OPx3kPompJ7SiV52LzSPCNpBJcnaM5yqTK51J-naE64IJlkIp-hi2HYEUKl0Pk5mjHJKaGaztHXxoQtRKiw38dgLDTN2JiAjbVjm67ouz3uHG6NDV1fmy3g1m_D9Pf72pc-duGAnbFppw-ONeAAPQQ3Dkm2BhMibqHyJsKArQmV7_rQRbBHjUt05kwzwNXPXqCP56fN6jVbv7-8rR7XmRVKxEzznJZWVE7p3NklU4pUllNNmFmWgkguOaMKLHeSEFUyDbxiQijDkjFNgC_Q3aSbYgxDAFf0wbcmHApKimOPxbHHgqRJPSb8ZsL7sUze_-Df4hJwOwGx9tBCsevGsE8B_pf7BpKufow</recordid><startdate>201601</startdate><enddate>201601</enddate><creator>Pohl, Julia</creator><creator>Hendgen-Cotta, Ulrike R.</creator><creator>Rammos, Christos</creator><creator>Luedike, Peter</creator><creator>Mull, Elena</creator><creator>Stoppe, Christian</creator><creator>Jülicher, Karen</creator><creator>Lue, Hongqi</creator><creator>Merx, Marc</creator><creator>Kelm, Malte</creator><creator>Bernhagen, Jürgen</creator><creator>Rassaf, Tienush</creator><general>Schattauer GmbH</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201601</creationdate><title>Targeted intracellular accumulation of macrophage migration inhibitory factor in the reperfused heart mediates cardioprotection</title><author>Pohl, Julia ; Hendgen-Cotta, Ulrike R. ; Rammos, Christos ; Luedike, Peter ; Mull, Elena ; Stoppe, Christian ; Jülicher, Karen ; Lue, Hongqi ; Merx, Marc ; Kelm, Malte ; Bernhagen, Jürgen ; Rassaf, Tienush</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-9351bc4df795fc82770dc31902a8b406363217ec3f6007b29e3d2447a2fac90e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aconitate Hydratase - metabolism</topic><topic>Animals</topic><topic>Atherosclerosis and Ischaemic Disease</topic><topic>Cell Line</topic><topic>Disease Models, Animal</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>Intramolecular Oxidoreductases - deficiency</topic><topic>Intramolecular Oxidoreductases - genetics</topic><topic>Intramolecular Oxidoreductases - metabolism</topic><topic>Macrophage Migration-Inhibitory Factors - deficiency</topic><topic>Macrophage Migration-Inhibitory Factors - genetics</topic><topic>Macrophage Migration-Inhibitory Factors - metabolism</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myocardial Infarction - genetics</topic><topic>Myocardial Infarction - metabolism</topic><topic>Myocardial Infarction - pathology</topic><topic>Myocardial Infarction - prevention & control</topic><topic>Myocardial Reperfusion Injury - genetics</topic><topic>Myocardial Reperfusion Injury - metabolism</topic><topic>Myocardial Reperfusion Injury - pathology</topic><topic>Myocardial Reperfusion Injury - prevention & control</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Nitrosation</topic><topic>Oxidative Stress</topic><topic>Protein Processing, Post-Translational</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pohl, Julia</creatorcontrib><creatorcontrib>Hendgen-Cotta, Ulrike R.</creatorcontrib><creatorcontrib>Rammos, Christos</creatorcontrib><creatorcontrib>Luedike, Peter</creatorcontrib><creatorcontrib>Mull, Elena</creatorcontrib><creatorcontrib>Stoppe, Christian</creatorcontrib><creatorcontrib>Jülicher, Karen</creatorcontrib><creatorcontrib>Lue, Hongqi</creatorcontrib><creatorcontrib>Merx, Marc</creatorcontrib><creatorcontrib>Kelm, Malte</creatorcontrib><creatorcontrib>Bernhagen, Jürgen</creatorcontrib><creatorcontrib>Rassaf, Tienush</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pohl, Julia</au><au>Hendgen-Cotta, Ulrike R.</au><au>Rammos, Christos</au><au>Luedike, Peter</au><au>Mull, Elena</au><au>Stoppe, Christian</au><au>Jülicher, Karen</au><au>Lue, Hongqi</au><au>Merx, Marc</au><au>Kelm, Malte</au><au>Bernhagen, Jürgen</au><au>Rassaf, Tienush</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted intracellular accumulation of macrophage migration inhibitory factor in the reperfused heart mediates cardioprotection</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2016-01</date><risdate>2016</risdate><volume>115</volume><issue>1</issue><spage>200</spage><epage>212</epage><pages>200-212</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><abstract>Summary
S
-nitrosation of macrophage migration inhibitory factor (MIF) has been shown to be cytoprotective in myocardial ischaemia/reperfusion (I/R) injury. Since the exact mechanism of action is unknown, we here characterise the cardioprotective effects of targeted intracellular accumulation of MIF in myocardial I/R injury. We used different
in vivo
,
ex vivo
and
in vitro
models of myocardial I/R and hypoxia/reoxyge-nation (H/R) injury to determine MIF levels by immunoblots and ELISA in different phases of reperfusion and reoxygenation, respectively. We discovered a rapid decrease of cardiac MIF that was specific to the early phase of reperfusion. Posttranslational modification of MIF via
S
-nitrosation – proofed by a modified version of the Biotin Switch Assay – prevented this rapid decrease, leading to a targeted intracellular accumulation of MIF in the early phase of reperfusion. Intracellular MIF accumulation preserved the intracellular ability of MIF to reduce oxidative stress as shown by hydrogen peroxide and aconitase activity measurements. Infarct size measurements by TTC staining showed an overall enhanced cardioprotective effect of this protein by reduction of reperfusion injury. In summary, we have unravelled a novel mechanism of MIF-mediated cardioprotection. Targeted intra-cellular accumulation of MIF by
S
-nitrosation may offer a novel therapeutic approach in the treatment of myocardial I/R-injury.</abstract><cop>Schattauer</cop><pub>Schattauer GmbH</pub><pmid>26310191</pmid><doi>10.1160/TH15-05-0436</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Thrombosis and haemostasis, 2016-01, Vol.115 (1), p.200-212 |
| issn | 0340-6245 2567-689X |
| language | eng |
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| source | MEDLINE; Thieme Connect Journals |
| subjects | Aconitate Hydratase - metabolism Animals Atherosclerosis and Ischaemic Disease Cell Line Disease Models, Animal Hydrogen Peroxide - metabolism Intramolecular Oxidoreductases - deficiency Intramolecular Oxidoreductases - genetics Intramolecular Oxidoreductases - metabolism Macrophage Migration-Inhibitory Factors - deficiency Macrophage Migration-Inhibitory Factors - genetics Macrophage Migration-Inhibitory Factors - metabolism Male Mice, Inbred C57BL Mice, Knockout Myocardial Infarction - genetics Myocardial Infarction - metabolism Myocardial Infarction - pathology Myocardial Infarction - prevention & control Myocardial Reperfusion Injury - genetics Myocardial Reperfusion Injury - metabolism Myocardial Reperfusion Injury - pathology Myocardial Reperfusion Injury - prevention & control Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Nitrosation Oxidative Stress Protein Processing, Post-Translational Time Factors |
| title | Targeted intracellular accumulation of macrophage migration inhibitory factor in the reperfused heart mediates cardioprotection |
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