Manganese Superoxide Dismutase in Healthy Human Pleural Mesothelium and in Malignant Pleural Mesothelioma

作者：Katriina Kahlos, Sisko Anttila, Tiina M. Asikainen, K Kinnula, Kari O. Raivio, Karin V. Mattson, Kaija Linnainmaa, Vuokko L. Kinnula · 发表于：American Journal of Respiratory Cell and Molecular Biology · 年份：1998 · DOI：10.1165/ajrcmb.18.4.2943 · 被引用次数：75 · 研究领域：Occupational and environmental lung diseases、Aluminum toxicity and tolerance in plants and animals、Thallium and Germanium Studies

We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelial cells (Met5A), and in two human mesothelioma cell lines (M14K and M38K) established from the tumor tissue of mesothelioma patients. There was no MnSOD immunoreactivity in five of the six samples of healthy pleural mesothelium, whereas MnSOD immunoreactivity was high in the tumor cells in all the mesothelioma samples. Northern blotting, immunohistochemistry, Western blotting, and specific activity measurements showed lower MnSOD in the nonmalignant Met5A mesothelial cells than in the M14K and M38K mesothelioma cells. In additional experiments the mesothelial and mesothelioma cells were exposed to menadione, which generates superoxide intracellularly, and to epirubicin, a cytotoxic drug commonly used to treat mesothelioma. The M38K mesothelioma cells were most resistant to menadione and epirubicin when assessed by LDH release or by adenine nucleotide (ATP, ADP, and AMP) depletion. These same cells showed not only the highest MnSOD levels, but also the highest mRNA levels and activities of catalase, whereas glutathione peroxidase and glutathione reductase levels did not differ significan...