Venkataraman Sujatha, Wagner Brett A, Jiang Xiaohong, Wang Hong P, Schafer Freya Q, Ritchie Justine M, Patrick Burns C, Oberley Larry W, Buettner Garry R
Department of Radiation Oncology, Free Radical and Radiation Biology Program, EMRB 68, The University of Iowa, Iowa City, IA 52242-1101, USA.
Free Radic Res. 2004 Oct;38(10):1119-32. doi: 10.1080/10715760400010470.
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 degrees 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.
据推测，细胞暴露于高温会导致活性氧（ROS）通量增加，主要是超氧阴离子自由基，并且增加抗氧化酶水平将保护细胞免受这些ROS的毒性影响。在本研究中，前列腺癌细胞系PC-3及其过表达锰超氧化物歧化酶（MnSOD）的克隆细胞接受了高温处理（43℃，1小时）。MnSOD表达增加导致线粒体膜电位（MMP）升高。通过乌头酸酶失活、脂质过氧化和H2O2形成以及细胞存活率降低来确定，PC-3细胞的高温暴露导致ROS产生增加。相比之下，与PC-3野生型细胞相比，过表达MnSOD的PC-3细胞具有更少的ROS产生、更少的脂质过氧化和更高的细胞存活率。由于MnSOD可清除超氧化物，这些结果表明超氧自由基或其反应产物是与高温相关的部分细胞毒性的原因，并且MnSOD可减少细胞损伤，从而提高耐热性。
