XMU-MP-1 protects heart from ischemia/reperfusion injury in mice through modulating Mst1/AMPK pathway
Up to now, there are few therapeutic approaches available to protect heart from ischemia/reperfusion (I/R) injury. The present work was designed to examine the protection of XMU-MP-1, an inhibitor of mammalian sterile 20-like kinase 1 (Mst1), against myocardial I/R injury in mice and investigate the...
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| Veröffentlicht in: | European journal of pharmacology 2022-03, Vol.919, p.174801-174801, Article 174801 |
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| creator | Liu, Yu Chu, Guojun Shen, Wenzhi Zhang, Yuefan Xu, Wei Yu, Yongsheng |
| description | Up to now, there are few therapeutic approaches available to protect heart from ischemia/reperfusion (I/R) injury. The present work was designed to examine the protection of XMU-MP-1, an inhibitor of mammalian sterile 20-like kinase 1 (Mst1), against myocardial I/R injury in mice and investigate the underlying molecular mechanisms. The wild-type and Mst1 (−/−) mice were exposed to I/R injury and treated with XMU-MP-1 immediately after reperfusion. Treatment with XMU-MP-1 reduced infarct size, attenuated apoptosis and necrosis, and preserved cardiac function of I/R mice. XMU-MP-1 mitigated mitochondrial dysfunction in myocardium of I/R mice. In addition, XMU-MP-1 stimulated M2 macrophage polarization and suppressed inflammation in myocardium of I/R mice. Mst1 deficiency had similar benefits on myocardial I/R injury and XMU-MP-1 treatment did not provide further protection against I/R injury in Mst1 (−/−) mice. Both treatment with XMU-MP-1 and Mst1 deficiency promoted the activation of AMPKα in myocardium of I/R mice. More importantly, administration of Compound C (a specific AMPK signaling blocker) blunted the protective effects of XMU-MP-1 on myocardial I/R injury. Collectively, reperfusion therapy with XMU-MP-1 mitigated myocardial I/R injury and preserved myocardial function in mice through modulating Mst1/AMPK pathway. |
| doi_str_mv | 10.1016/j.ejphar.2022.174801 |
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The present work was designed to examine the protection of XMU-MP-1, an inhibitor of mammalian sterile 20-like kinase 1 (Mst1), against myocardial I/R injury in mice and investigate the underlying molecular mechanisms. The wild-type and Mst1 (−/−) mice were exposed to I/R injury and treated with XMU-MP-1 immediately after reperfusion. Treatment with XMU-MP-1 reduced infarct size, attenuated apoptosis and necrosis, and preserved cardiac function of I/R mice. XMU-MP-1 mitigated mitochondrial dysfunction in myocardium of I/R mice. In addition, XMU-MP-1 stimulated M2 macrophage polarization and suppressed inflammation in myocardium of I/R mice. Mst1 deficiency had similar benefits on myocardial I/R injury and XMU-MP-1 treatment did not provide further protection against I/R injury in Mst1 (−/−) mice. Both treatment with XMU-MP-1 and Mst1 deficiency promoted the activation of AMPKα in myocardium of I/R mice. More importantly, administration of Compound C (a specific AMPK signaling blocker) blunted the protective effects of XMU-MP-1 on myocardial I/R injury. Collectively, reperfusion therapy with XMU-MP-1 mitigated myocardial I/R injury and preserved myocardial function in mice through modulating Mst1/AMPK pathway.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2022.174801</identifier><identifier>PMID: 35123978</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>AMP-Activated protein kinase ; AMP-Activated Protein Kinases - metabolism ; Animals ; Apoptosis - drug effects ; Cardiotonic Agents - chemistry ; Cardiotonic Agents - pharmacology ; Cardiotonic Agents - therapeutic use ; Disease Models, Animal ; Fibrosis ; Inflammation ; Male ; Mammalian sterile 20-like kinase 1 ; Mice ; Mice, Inbred C57BL ; Mitochondrial function ; Myocardial Reperfusion Injury - prevention & control ; Myocytes, Cardiac - drug effects ; Signal Transduction - drug effects ; Sulfonamides - chemistry ; Sulfonamides - pharmacology ; Sulfonamides - therapeutic use</subject><ispartof>European journal of pharmacology, 2022-03, Vol.919, p.174801-174801, Article 174801</ispartof><rights>2022 Elsevier B.V.</rights><rights>Copyright © 2022 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-48a0ce8b00e0d2fd6d83cba96a2880e36ee88416c294488c84afd6afdd6d5c393</citedby><cites>FETCH-LOGICAL-c428t-48a0ce8b00e0d2fd6d83cba96a2880e36ee88416c294488c84afd6afdd6d5c393</cites><orcidid>0000-0001-5238-1181</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2022.174801$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35123978$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Chu, Guojun</creatorcontrib><creatorcontrib>Shen, Wenzhi</creatorcontrib><creatorcontrib>Zhang, Yuefan</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Yu, Yongsheng</creatorcontrib><title>XMU-MP-1 protects heart from ischemia/reperfusion injury in mice through modulating Mst1/AMPK pathway</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Up to now, there are few therapeutic approaches available to protect heart from ischemia/reperfusion (I/R) injury. The present work was designed to examine the protection of XMU-MP-1, an inhibitor of mammalian sterile 20-like kinase 1 (Mst1), against myocardial I/R injury in mice and investigate the underlying molecular mechanisms. The wild-type and Mst1 (−/−) mice were exposed to I/R injury and treated with XMU-MP-1 immediately after reperfusion. Treatment with XMU-MP-1 reduced infarct size, attenuated apoptosis and necrosis, and preserved cardiac function of I/R mice. XMU-MP-1 mitigated mitochondrial dysfunction in myocardium of I/R mice. In addition, XMU-MP-1 stimulated M2 macrophage polarization and suppressed inflammation in myocardium of I/R mice. Mst1 deficiency had similar benefits on myocardial I/R injury and XMU-MP-1 treatment did not provide further protection against I/R injury in Mst1 (−/−) mice. Both treatment with XMU-MP-1 and Mst1 deficiency promoted the activation of AMPKα in myocardium of I/R mice. More importantly, administration of Compound C (a specific AMPK signaling blocker) blunted the protective effects of XMU-MP-1 on myocardial I/R injury. Collectively, reperfusion therapy with XMU-MP-1 mitigated myocardial I/R injury and preserved myocardial function in mice through modulating Mst1/AMPK pathway.</description><subject>AMP-Activated protein kinase</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Cardiotonic Agents - chemistry</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Cardiotonic Agents - therapeutic use</subject><subject>Disease Models, Animal</subject><subject>Fibrosis</subject><subject>Inflammation</subject><subject>Male</subject><subject>Mammalian sterile 20-like kinase 1</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitochondrial function</subject><subject>Myocardial Reperfusion Injury - prevention & control</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Signal Transduction - drug effects</subject><subject>Sulfonamides - chemistry</subject><subject>Sulfonamides - pharmacology</subject><subject>Sulfonamides - therapeutic use</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMoun78A5EcvXQ3SbNtchFE_EIX9-CCt5BNpzZl-2GSKvvvzVL1KMMwl2dmeB-EzimZUkKzWT2Fuq-0mzLC2JTmXBC6hyZU5DIhOWX7aEII5QmTUh6hY-9rQshcsvkhOkrnlKUyFxMEb4tVslgmFPeuC2CCxxVoF3DpugZbbyporJ456MGVg7ddi21bD24bB26sARwq1w3vFW66YtjoYNt3vPCBzq4Xyyfc61B96e0pOij1xsPZzzxBq7vb15uH5Pnl_vHm-jkxnImQcKGJAbEmBEjByiIrRGrWWmaaCUEgzQCE4DQzTHIuhBFcRyh2JOcmlekJuhzvxjAfA_igmhgBNhvdQjd4xbJYLGU5iygfUeM67x2Uqne20W6rKFE7wapWo2C1E6xGwXHt4ufDsG6g-Fv6NRqBqxGAmPPTglPeWGgNFNZFvaro7P8fvgHe_46N</recordid><startdate>20220315</startdate><enddate>20220315</enddate><creator>Liu, Yu</creator><creator>Chu, Guojun</creator><creator>Shen, Wenzhi</creator><creator>Zhang, Yuefan</creator><creator>Xu, Wei</creator><creator>Yu, Yongsheng</creator><general>Elsevier B.V</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><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5238-1181</orcidid></search><sort><creationdate>20220315</creationdate><title>XMU-MP-1 protects heart from ischemia/reperfusion injury in mice through modulating Mst1/AMPK pathway</title><author>Liu, Yu ; Chu, Guojun ; Shen, Wenzhi ; Zhang, Yuefan ; Xu, Wei ; Yu, Yongsheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-48a0ce8b00e0d2fd6d83cba96a2880e36ee88416c294488c84afd6afdd6d5c393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>AMP-Activated protein kinase</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Cardiotonic Agents - chemistry</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>Cardiotonic Agents - therapeutic use</topic><topic>Disease Models, Animal</topic><topic>Fibrosis</topic><topic>Inflammation</topic><topic>Male</topic><topic>Mammalian sterile 20-like kinase 1</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mitochondrial function</topic><topic>Myocardial Reperfusion Injury - prevention & control</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Signal Transduction - drug effects</topic><topic>Sulfonamides - chemistry</topic><topic>Sulfonamides - pharmacology</topic><topic>Sulfonamides - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Chu, Guojun</creatorcontrib><creatorcontrib>Shen, Wenzhi</creatorcontrib><creatorcontrib>Zhang, Yuefan</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Yu, Yongsheng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Yu</au><au>Chu, Guojun</au><au>Shen, Wenzhi</au><au>Zhang, Yuefan</au><au>Xu, Wei</au><au>Yu, Yongsheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>XMU-MP-1 protects heart from ischemia/reperfusion injury in mice through modulating Mst1/AMPK pathway</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2022-03-15</date><risdate>2022</risdate><volume>919</volume><spage>174801</spage><epage>174801</epage><pages>174801-174801</pages><artnum>174801</artnum><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract>Up to now, there are few therapeutic approaches available to protect heart from ischemia/reperfusion (I/R) injury. The present work was designed to examine the protection of XMU-MP-1, an inhibitor of mammalian sterile 20-like kinase 1 (Mst1), against myocardial I/R injury in mice and investigate the underlying molecular mechanisms. The wild-type and Mst1 (−/−) mice were exposed to I/R injury and treated with XMU-MP-1 immediately after reperfusion. Treatment with XMU-MP-1 reduced infarct size, attenuated apoptosis and necrosis, and preserved cardiac function of I/R mice. XMU-MP-1 mitigated mitochondrial dysfunction in myocardium of I/R mice. In addition, XMU-MP-1 stimulated M2 macrophage polarization and suppressed inflammation in myocardium of I/R mice. Mst1 deficiency had similar benefits on myocardial I/R injury and XMU-MP-1 treatment did not provide further protection against I/R injury in Mst1 (−/−) mice. Both treatment with XMU-MP-1 and Mst1 deficiency promoted the activation of AMPKα in myocardium of I/R mice. More importantly, administration of Compound C (a specific AMPK signaling blocker) blunted the protective effects of XMU-MP-1 on myocardial I/R injury. Collectively, reperfusion therapy with XMU-MP-1 mitigated myocardial I/R injury and preserved myocardial function in mice through modulating Mst1/AMPK pathway.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>35123978</pmid><doi>10.1016/j.ejphar.2022.174801</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5238-1181</orcidid></addata></record> |
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| subjects | AMP-Activated protein kinase AMP-Activated Protein Kinases - metabolism Animals Apoptosis - drug effects Cardiotonic Agents - chemistry Cardiotonic Agents - pharmacology Cardiotonic Agents - therapeutic use Disease Models, Animal Fibrosis Inflammation Male Mammalian sterile 20-like kinase 1 Mice Mice, Inbred C57BL Mitochondrial function Myocardial Reperfusion Injury - prevention & control Myocytes, Cardiac - drug effects Signal Transduction - drug effects Sulfonamides - chemistry Sulfonamides - pharmacology Sulfonamides - therapeutic use |
| title | XMU-MP-1 protects heart from ischemia/reperfusion injury in mice through modulating Mst1/AMPK pathway |
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