Kinnula V L, Pietarinen-Runtti P, Raivio K, Kahlos K, Pelin K, Mattson K, Linnainmaa K
University of Oulu, Department of Internal Medicine, University of Helsinki, Finland.
Free Radic Biol Med. 1996;21(4):527-32. doi: 10.1016/0891-5849(96)00049-4.
Mesothelioma is a malignant pleural or intraperitoneal tumor attributable to asbestos exposure in more than 80% of the cases. Manganese superoxide dismutase (MnSOD), a mitochondrial superoxide radical scavenging enzyme, is low in most tumors but is known to be induced by asbestos fibers and certain cytokines. Induction of MnSOD may be associated in asbestos-related pulmonary diseases in vivo. We investigated here MnSOD specific activity and MnSOD mRNA level using healthy human lung tissue, SV40-transformed human pleural mesothelial cells (Met5A), and six human malignant mesothelioma cell line cells. Total SOD (CuZnSOD + MnSOD) and MnSOD activities were 20.0 +/- 4.8 U/mg protein and 3.2 +/- 1.2 U/mg protein in healthy human lung tissue, and 25.6 +/- 10.7 U/mg and 3.8 +/- 1.0 U/mg in Met5A cells, respectively. In four mesothelioma cell lines MnSOD activity was significantly elevated, the highest activity (30.1 +/- 8.2 U/mg) was almost 10-fold compared to the activity in Met5A cells. The steady state mRNA level of MnSOD was low in Met5A cells and markedly higher in all mesothelioma cell lines roughly in proportion with enzyme activities. Cytotoxicity experiments, which were conducted in four cell lines, indicated that cells containing high MnSOD mRNA level and activity were resistant to the mitochondrial superoxide-producing agent menadione. In conclusion, our results suggest that human mesothelioma may express high levels of MnSOD, which is associated with high oxidant resistance of these cells.
间皮瘤是一种恶性胸膜或腹膜肿瘤，80%以上的病例可归因于石棉暴露。锰超氧化物歧化酶（MnSOD）是一种线粒体超氧化物自由基清除酶，在大多数肿瘤中含量较低，但已知可被石棉纤维和某些细胞因子诱导。MnSOD的诱导可能与体内石棉相关的肺部疾病有关。我们在此使用健康人肺组织、SV40转化的人胸膜间皮细胞（Met5A）和六种人恶性间皮瘤细胞系细胞研究了MnSOD的比活性和MnSOD mRNA水平。健康人肺组织中总超氧化物歧化酶（CuZnSOD + MnSOD）和MnSOD活性分别为20.0 +/- 4.8 U/mg蛋白质和3.2 +/- 1.2 U/mg蛋白质，Met5A细胞中分别为25.6 +/- 10.7 U/mg和3.8 +/- 1.0 U/mg。在四种间皮瘤细胞系中，MnSOD活性显著升高，最高活性（30.1 +/- 8.2 U/mg）几乎是Met5A细胞中活性的10倍。MnSOD的稳态mRNA水平在Met5A细胞中较低，而在所有间皮瘤细胞系中明显较高，大致与酶活性成比例。在四种细胞系中进行的细胞毒性实验表明，含有高MnSOD mRNA水平和活性的细胞对产生线粒体超氧化物的药物甲萘醌具有抗性。总之，我们的结果表明，人恶性间皮瘤可能表达高水平的MnSOD，这与这些细胞的高抗氧化性有关。
