Redox gene therapy for ischemia/reperfusion injury of the liver reduces AP1 and NF-kappaB activation

Nat Med. 1998 Jun;4(6):698-704. doi: 10.1038/nm0698-698.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Relb protein, mouse
  • Transcription Factor AP-1
  • Transcription Factors
  • Transcription Factor RelB
  • Superoxide Dismutase