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 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.
Zwacka
R M
RM
Department of Anatomy and Cell Biology, University of Iowa, Iowa City 52242, USA.
Zhou
W
W
Zhang
Y
Y
Darby
C J
CJ
Dudus
L
L
Halldorson
J
J
Oberley
L
L
Engelhardt
J F
JF
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
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