Overexpression of Manganese Superoxide Dismutase Promotes the Survival of Prostate Cancer Cells Exposed to Hyperthermia |
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Authors: | Sujatha Venkataraman Brett A Wagner Xiaohong Jiang Hong P Wang Freya Q Schafer Justine M Ritchie |
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Institution: | 1. ESR Facility, EMRB 68, The University of Iowa, 52242, Iowa City, IA, USASujatha-venkataraman@uiowa.eduSujatha-venkataraman@uiowa.edu;4. Department of Internal Medicine, C32GH, The University of Iowa, 52242, Iowa City, IA, USA;5. Department of Radiation Oncology, Free Radical and Radiation Biology Program, EMRB 68, The University of Iowa, 52242-1101, Iowa City, IA, USA;6. ESR Facility, EMRB 68, The University of Iowa, 52242, Iowa City, IA, USA;7. Department of Biostatistics, C22GH, The University of Iowa, 52242, Iowa City, IA, USA |
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Abstract: | It has been hypothesized that exposure of cells to hyperthermia results in an increased flux of reactive oxygen species (ROS), primarily superoxide anion radicals, and that increasing antioxidant enzyme levels will result in protection of cells from the toxicity of these ROS. In this study, the prostate cancer cell line, PC-3, and its manganese superoxide dismutase (MnSOD)-overexpressing clones were subjected to hyperthermia (43°C, 1?h). Increased expression of MnSOD increased the mitochondrial membrane potential (MMP). Hyperthermic exposure of PC-3 cells resulted in increased ROS production, as determined by aconitase inactivation, lipid peroxidation, and H2O2 formation with a reduction in cell survival. In contrast, PC-3 cells overexpressing MnSOD had less ROS production, less lipid peroxidation, and greater cell survival compared to PC-3 Wt cells. Since MnSOD removes superoxide, these results suggest that superoxide free radical or its reaction products are responsible for part of the cytotoxicity associated with hyperthermia and that MnSOD can reduce cellular injury and thereby enhance heat tolerance. |
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Keywords: | Superoxide dismutase Hyperthermia Aconitase Lipid peroxidation Heat shock protein Electron paramagnetic resonance |
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