Journal article
Manganese Superoxide Dismutase-Mediated Gene Expression in Radiation-Induced Adaptive Responses
Molecular and cellular biology, Vol.23(7), pp.2362-2378
04/01/2003
DOI: 10.1128/MCB.23.7.2362-2378.2003
PMCID: PMC150726
PMID: 12640121
Abstract
Antioxidant enzymes are critical in oxidative stress responses. Radioresistant variants isolated from MCF-7 human carcinoma cells following fractionated ionizing radiation (MCF+FIR cells) or overexpression of manganese superoxide dismutase (MCF+SOD cells) demonstrated dose-modifying factors at 10% isosurvival of 1.8 and 2.3, respectively. MCF+FIR and MCF-7 cells (exposed to single-dose radiation) demonstrated 5- to 10-fold increases in MnSOD activity, mRNA, and immunoreactive protein. Radioresistance in MCF+FIR and MCF+SOD cells was reduced following expression of antisense MnSOD. DNA microarray analysis and immunoblotting identified p21, Myc, 14-3-3 zeta, cyclin A, cyclin B1, and GADD153 as genes constitutively overexpressed (2- to 10-fold) in both MCF+FIR and MCF+SOD cells. Radiation-induced expression of these six genes was suppressed in fibroblasts from
Sod2
knockout mice (−/−) as well as in MCF+FIR and MCF+SOD cells expressing antisense MnSOD. Inhibiting NF-κB transcriptional activity in MCF+FIR cells, by using mutant IκBα, inhibited radioresistance as well as reducing steady-state levels of MnSOD, 14-3-3 zeta, GADD153, cyclin A, and cyclin B1 mRNA. In contrast, mutant IκBα was unable to inhibit radioresistance or reduce 14-3-3 zeta, GADD153, cyclin A, and cyclin B1 mRNAs in MCF+SOD cells, where MnSOD overexpression was independent of NF-κB. These results support the hypothesis that NF-κB is capable of regulating the expression of MnSOD, which in turn is capable of increasing the expression of genes that participate in radiation-induced adaptive responses.
Details
- Title: Subtitle
- Manganese Superoxide Dismutase-Mediated Gene Expression in Radiation-Induced Adaptive Responses
- Creators
- Guozheng Guo - City Of Hope National Medical CenterYan Yan-Sanders - United States Food and Drug AdministrationBeverly D. Lyn-Cook - United States Food and Drug AdministrationTieli Wang - City Of Hope National Medical CenterDaniel Tamae - City Of Hope National Medical CenterJulie Ogi - City Of Hope National Medical CenterAlexander Khaletskiy - City Of Hope National Medical CenterZhongkui Li - Molecular & Cellular OncologyChristine Weydert - University of IowaJeffrey A. Longmate - Radiation Biology, Division of Radiation Oncology, Biostatistics, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010, Division of Molecular Epidemiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa 52242, Neurology and Neurological Sciences, Stanford University, Palo Alto, California 94304Ting-Ting Huang - Stanford UniversityDouglas R. Spitz - University of IowaLarry W. Oberley - University of IowaJian Jian Li - City Of Hope National Medical Center
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.23(7), pp.2362-2378
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/MCB.23.7.2362-2378.2003
- PMID
- 12640121
- PMCID
- PMC150726
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 04/01/2003
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312980302771
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