Journal article
Subcellular site of superoxide dismutase expression differentially controls AP-1 activity and injury in mouse liver following ischemia/reperfusion
Hepatology (Baltimore, Md.), Vol.33(4), pp.902-914
2001
DOI: 10.1053/jhep.2001.23073
PMID: 11283855
Abstract
Acute damage following ischemia and reperfusion (I/R) in the liver is in part caused by the generation of reactive oxygen species, such as superoxides, during the reperfusion event. Gene therapy directed at attenuating mitochondrial superoxide production following warm I/R injury in the liver has demonstrated great promise in reducing acute hepatocellular damage. In the present study, we have compared the therapeutic effects of ectopic expression of mitochondrial (MnSOD) and cytoplasmic (Cu/ZnSOD) superoxide dismutase using recombinant adenoviral vectors for reducing I/R damage in the liver. Consistent with previous observations, recombinant adenoviral delivery of MnSOD to the liver significantly attenuated both acute liver damage and AP‐1 activation following I/R injury to the livers of mice. However, ectopic expression of Cu/ZnSOD diminished neither I/R‐induced elevations in serum alanine transaminase (ALT) nor AP‐1 activation. Interestingly, baseline activation of AP‐1 before I/R‐induced injury was seen in livers infected with recombinant Ad.Cu/ZnSOD, but not Ad.MnSOD or Ad.LacZ, vectors. The level of Cu/ZnSOD‐induced AP‐1 activation was significantly reduced by ablation of Kupffer cells or by coexpression of catalase, suggesting that increased H2O2 production facilitated by Cu/ZnSOD in hepatocytes and/or Kupffer cells may be responsible for AP‐1 activation. In vitro reconstitution studies using hepatocyte and macrophage cell lines demonstrated that Cu/ZnSOD overexpression induces AP‐1 in both cell types, and that secretion of a Cu/ZnSOD‐induced macrophage factor is capable of elevating AP‐1 in hepatocytes. In summary, our findings demonstrate that subcellular sites of superoxide production in the liver can differentially affect the outcome of I/R injury in the liver and selectively influence AP‐1 activation.
Details
- Title: Subtitle
- Subcellular site of superoxide dismutase expression differentially controls AP-1 activity and injury in mouse liver following ischemia/reperfusion
- Creators
- Weihong Zhou - Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City. IA, United StatesYulong Zhang - Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City. IA, United StatesMicaela S HOSCH - Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City. IA, United StatesAmie LANG - Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City. IA, United StatesRalf M ZWACKA - Department of Oncology, University of Edinburgh, Edinburgh, Scotland, United KingdomJohn F ENGELHARDT - Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City. IA, United States
- Resource Type
- Journal article
- Publication Details
- Hepatology (Baltimore, Md.), Vol.33(4), pp.902-914
- DOI
- 10.1053/jhep.2001.23073
- PMID
- 11283855
- NLM abbreviation
- Hepatology
- ISSN
- 0270-9139
- eISSN
- 1527-3350
- Publisher
- Wiley; Hoboken, NJ
- Language
- English
- Date published
- 2001
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025474302771
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