Journal article
Stat3 confers resistance against hypoxia/reoxygenation-induced oxidative injury in hepatocytes through upregulation of Mn-SOD
Journal of hepatology, Vol.41(6), pp.957-965
2004
DOI: 10.1016/j.jhep.2004.08.019
PMID: 15582129
Abstract
Hypoxia/reoxygenation (H/R) causes oxidative stress to the cell and induces apoptotic cell death. Signal transducer and activator of transcription-3 (Stat3) is one of the most important molecules involved in the initiation of liver development and regeneration, and has recently been shown to protect cells against various pathogens. In order to investigate the hepatoprotective effects of Stat3, we examined whether it protects against H/R-induced injury in primary hepatocytes.
Primary cultured hepatocytes were prepared from SD rats. Adenoviruses and cytokines were added 2 days and 1
h prior to the H/R insult, respectively. Hepatocytes and culture media were harvested for the assays before and after H/R insult.
Interleukin-6 and cardiotropin-1, which may function mainly through Stat3 activation, protected cells from H/R-induced apoptosis. Adenoviral overexpression of the constitutively activated form of Stat3 (Stat3-C) reduced H/R-induced apoptosis as well as generation of reactive oxygen species (ROS) in hepatocytes. Interestingly, Stat3-C induced Mn-SOD, but not Cu/Zn-SOD, both at the protein and mRNA levels. Overexpression of Mn-SOD significantly reduced H/R-induced ROS and apoptosis by inhibiting redox-sensitive activation of caspase-3 activity.
Stat3 protects hepatocytes from H/R-induced cell injury at least partly by upregulating Mn-SOD and inactivating caspase-3.
Details
- Title: Subtitle
- Stat3 confers resistance against hypoxia/reoxygenation-induced oxidative injury in hepatocytes through upregulation of Mn-SOD
- Creators
- Keita Terui - Bioengineering Laboratory, Department of Innovative Surgery, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya, Tokyo 157-8535, JapanShin Enosawa - Bioengineering Laboratory, Department of Innovative Surgery, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya, Tokyo 157-8535, JapanSanae Haga - Bioengineering Laboratory, Department of Innovative Surgery, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya, Tokyo 157-8535, JapanHui Qi Zhang - Bioengineering Laboratory, Department of Innovative Surgery, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya, Tokyo 157-8535, JapanHiroaki Kuroda - Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, JapanKatsunori Kouchi - Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, JapanTadashi Matsunaga - Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, JapanHideo Yoshida - Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, JapanJohn F Engelhardt - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA, USAKaikobad Irani - Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USANaomi Ohnuma - Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, JapanMichitaka Ozaki - Bioengineering Laboratory, Department of Innovative Surgery, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya, Tokyo 157-8535, Japan
- Resource Type
- Journal article
- Publication Details
- Journal of hepatology, Vol.41(6), pp.957-965
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.jhep.2004.08.019
- PMID
- 15582129
- ISSN
- 0168-8278
- eISSN
- 1600-0641
- Language
- English
- Date published
- 2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984047704302771
Metrics
24 Record Views