Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-kappaB activation
Liver transplantation is the only therapeutic strategy for many inherited and acquired diseases. The formation of reactive oxygen species following ischemia/reperfusion is a cause of hepatocellular injury during transplantation. This report describes the therapeutic application of mitochondrial supe...
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| Veröffentlicht in: | Nature medicine 1998-06, Vol.4 (6), p.698-704 |
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| creator | Zwacka, R M Zhou, W Zhang, Y Darby, C J Dudus, L Halldorson, J Oberley, L Engelhardt, J F |
| description | Liver transplantation is the only therapeutic strategy for many inherited and acquired diseases. The formation of reactive oxygen species following ischemia/reperfusion is a cause of hepatocellular injury during transplantation. This report describes the therapeutic application of mitochondrial superoxide dismutase gene transfer to the liver for acute ischemia/reperfusion injury. Recombinant adenoviral expression of mitochondrial superoxide dismutase in mouse liver prior to lobar ischemia/reperfusion significantly reduced acute liver damage and associated redox activation of both NF-kappaB and AP1. These immediate early transcription factors represent common pathways by which cells respond to environmental stress. This work provides the foundation for redox-mediated gene therapies directed at ameliorating ischemia/reperfusion injury and associated acute rejection in orthotopic liver transplantation. |
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The formation of reactive oxygen species following ischemia/reperfusion is a cause of hepatocellular injury during transplantation. This report describes the therapeutic application of mitochondrial superoxide dismutase gene transfer to the liver for acute ischemia/reperfusion injury. Recombinant adenoviral expression of mitochondrial superoxide dismutase in mouse liver prior to lobar ischemia/reperfusion significantly reduced acute liver damage and associated redox activation of both NF-kappaB and AP1. These immediate early transcription factors represent common pathways by which cells respond to environmental stress. This work provides the foundation for redox-mediated gene therapies directed at ameliorating ischemia/reperfusion injury and associated acute rejection in orthotopic liver transplantation.</description><identifier>ISSN: 1078-8956</identifier><identifier>PMID: 9623979</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Gene Expression - genetics ; Genetic Therapy ; Liver - blood supply ; Liver - enzymology ; Male ; Mice ; Mice, Nude ; Mitochondria, Liver - chemistry ; Mitochondria, Liver - enzymology ; Mitochondria, Liver - genetics ; NF-kappa B - antagonists & inhibitors ; NF-kappa B - metabolism ; Oxidation-Reduction ; Proto-Oncogene Proteins - metabolism ; Recombinant Proteins - genetics ; Reperfusion Injury - genetics ; Reperfusion Injury - therapy ; Superoxide Dismutase - analysis ; Superoxide Dismutase - genetics ; Superoxide Dismutase - physiology ; Transcription Factor AP-1 - antagonists & inhibitors ; Transcription Factor AP-1 - metabolism ; Transcription Factor RelB ; Transcription Factors ; Transcriptional Activation - genetics ; Transcriptional Activation - physiology ; Transgenes - genetics</subject><ispartof>Nature medicine, 1998-06, Vol.4 (6), p.698-704</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9623979$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zwacka, R M</creatorcontrib><creatorcontrib>Zhou, W</creatorcontrib><creatorcontrib>Zhang, Y</creatorcontrib><creatorcontrib>Darby, C J</creatorcontrib><creatorcontrib>Dudus, L</creatorcontrib><creatorcontrib>Halldorson, J</creatorcontrib><creatorcontrib>Oberley, L</creatorcontrib><creatorcontrib>Engelhardt, J F</creatorcontrib><title>Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-kappaB activation</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><description>Liver transplantation is the only therapeutic strategy for many inherited and acquired diseases. The formation of reactive oxygen species following ischemia/reperfusion is a cause of hepatocellular injury during transplantation. This report describes the therapeutic application of mitochondrial superoxide dismutase gene transfer to the liver for acute ischemia/reperfusion injury. Recombinant adenoviral expression of mitochondrial superoxide dismutase in mouse liver prior to lobar ischemia/reperfusion significantly reduced acute liver damage and associated redox activation of both NF-kappaB and AP1. These immediate early transcription factors represent common pathways by which cells respond to environmental stress. 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Zhou, W ; Zhang, Y ; Darby, C J ; Dudus, L ; Halldorson, J ; Oberley, L ; Engelhardt, J F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p539-cf36a3342207802d84792141ee43ccb5caf017a7e6e9ad04d887a6bae2167b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Gene Expression - genetics</topic><topic>Genetic Therapy</topic><topic>Liver - blood supply</topic><topic>Liver - enzymology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mitochondria, Liver - chemistry</topic><topic>Mitochondria, Liver - enzymology</topic><topic>Mitochondria, Liver - genetics</topic><topic>NF-kappa B - antagonists & inhibitors</topic><topic>NF-kappa B - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Recombinant Proteins - genetics</topic><topic>Reperfusion Injury - genetics</topic><topic>Reperfusion Injury - therapy</topic><topic>Superoxide Dismutase - analysis</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - physiology</topic><topic>Transcription Factor AP-1 - antagonists & inhibitors</topic><topic>Transcription Factor AP-1 - metabolism</topic><topic>Transcription Factor RelB</topic><topic>Transcription Factors</topic><topic>Transcriptional Activation - genetics</topic><topic>Transcriptional Activation - physiology</topic><topic>Transgenes - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zwacka, R M</creatorcontrib><creatorcontrib>Zhou, W</creatorcontrib><creatorcontrib>Zhang, Y</creatorcontrib><creatorcontrib>Darby, C J</creatorcontrib><creatorcontrib>Dudus, L</creatorcontrib><creatorcontrib>Halldorson, J</creatorcontrib><creatorcontrib>Oberley, L</creatorcontrib><creatorcontrib>Engelhardt, J F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Nature medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zwacka, R M</au><au>Zhou, W</au><au>Zhang, Y</au><au>Darby, C J</au><au>Dudus, L</au><au>Halldorson, J</au><au>Oberley, L</au><au>Engelhardt, J F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-kappaB activation</atitle><jtitle>Nature medicine</jtitle><addtitle>Nat Med</addtitle><date>1998-06</date><risdate>1998</risdate><volume>4</volume><issue>6</issue><spage>698</spage><epage>704</epage><pages>698-704</pages><issn>1078-8956</issn><abstract>Liver transplantation is the only therapeutic strategy for many inherited and acquired diseases. The formation of reactive oxygen species following ischemia/reperfusion is a cause of hepatocellular injury during transplantation. This report describes the therapeutic application of mitochondrial superoxide dismutase gene transfer to the liver for acute ischemia/reperfusion injury. Recombinant adenoviral expression of mitochondrial superoxide dismutase in mouse liver prior to lobar ischemia/reperfusion significantly reduced acute liver damage and associated redox activation of both NF-kappaB and AP1. These immediate early transcription factors represent common pathways by which cells respond to environmental stress. This work provides the foundation for redox-mediated gene therapies directed at ameliorating ischemia/reperfusion injury and associated acute rejection in orthotopic liver transplantation.</abstract><cop>United States</cop><pmid>9623979</pmid><tpages>7</tpages></addata></record> |
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| issn | 1078-8956 |
| language | eng |
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| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Animals Gene Expression - genetics Genetic Therapy Liver - blood supply Liver - enzymology Male Mice Mice, Nude Mitochondria, Liver - chemistry Mitochondria, Liver - enzymology Mitochondria, Liver - genetics NF-kappa B - antagonists & inhibitors NF-kappa B - metabolism Oxidation-Reduction Proto-Oncogene Proteins - metabolism Recombinant Proteins - genetics Reperfusion Injury - genetics Reperfusion Injury - therapy Superoxide Dismutase - analysis Superoxide Dismutase - genetics Superoxide Dismutase - physiology Transcription Factor AP-1 - antagonists & inhibitors Transcription Factor AP-1 - metabolism Transcription Factor RelB Transcription Factors Transcriptional Activation - genetics Transcriptional Activation - physiology Transgenes - genetics |
| title | Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-kappaB activation |
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