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Manganese superoxide dismutase in human pleural mesothelioma cell lines
V L Kinnula1, P Pietarinen-Runtti, K Raivio
1University of Oulu, Department of Internal Medicine, University of Helsinki, Finland.
Abstract:
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.
Insights
Malignant mesothelioma cells show significantly elevated Manganese Superoxide Dismutase (MnSOD) levels, an enzyme that scavenges superoxide radicals. High MnSOD expression in these cancer cells correlates with resistance to oxidative stress.
Area of Science:
- Oncology
- Biochemistry
- Environmental Health
Background:
- Mesothelioma is a cancer strongly linked to asbestos exposure.
- Manganese superoxide dismutase (MnSOD) is an enzyme that protects cells from oxidative damage.
- MnSOD is typically low in tumors but can be induced by asbestos.
Purpose of the Study:
- To investigate Manganese Superoxide Dismutase (MnSOD) specific activity and mRNA levels in human mesothelioma.
- To determine the relationship between MnSOD levels and asbestos-related diseases.
- To assess the role of MnSOD in mesothelioma cell resistance to oxidative stress.
Main Methods:
- Assessed MnSOD specific activity and mRNA levels in healthy lung tissue, normal mesothelial cells (Met5A), and mesothelioma cell lines.
- Measured total SOD and MnSOD activities.
- Conducted cytotoxicity experiments using menadione, an agent that produces mitochondrial superoxide.
Main Results:
- MnSOD activity and mRNA levels were significantly elevated in four out of six human mesothelioma cell lines compared to normal mesothelial cells.
- The highest MnSOD activity in mesothelioma cells was nearly 10-fold greater than in Met5A cells.
- Mesothelioma cells with high MnSOD levels exhibited resistance to menadione-induced cytotoxicity.
Conclusions:
- Human mesothelioma cells express high levels of MnSOD.
- Elevated MnSOD expression in mesothelioma is associated with increased resistance to oxidative stress.
- This suggests a potential role for MnSOD in the pathogenesis or progression of mesothelioma.