title: Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-kappaB activation.
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.
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa, Iowa City 52242, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Zwacka
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: C J
authors.initials: CJ
authors.lastname: Darby
authors.forename: L
authors.initials: L
authors.lastname: Dudus
authors.forename: J
authors.initials: J
authors.lastname: Halldorson
authors.forename: L
authors.initials: L
authors.lastname: Oberley
authors.forename: J F
authors.initials: JF
authors.lastname: Engelhardt
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000235:genetics; D015316:Genetic Therapy; D008099:Liver / Q000098:blood supply* / Q000201:enzymology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008930:Mitochondria, Liver / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010084:Oxidation-Reduction; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D015427:Reperfusion Injury / Q000235:genetics / Q000628:therapy*; D013482:Superoxide Dismutase / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051841:Transcription Factor RelB; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology; D019076:Transgenes / Q000235:genetics
chemical_list: D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C497594:Relb protein, mouse; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051841:Transcription Factor RelB; D013482:Superoxide Dismutase