Manganese superoxide dismutase in human pleural mesothelioma cell lines

Kinnula, Vuokko L.; Pietarinen-Runtti, Petra; Raivio, Kari O.; Kahlos, Katriina; Pelin, Katarina; Mattson, K.; Linnainmaa, Kaija

doi:10.1016/0891-5849(96)00049-4

Cited by 47 publications

(51 citation statements)

References 25 publications

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“…The results of the present study confirm our earlier finding on elevated MnSOD activity in M38K cells as compared to Met5A cells (Kinnula et al, 1996), the specific activity of MnSOD being 36.0 ± 3.4 U mg -1 protein in M38K cells and 1.8 ± 1.0 U mg -1 protein in Met5A cells. Moreover, the activities of the mitochondrial enzymes citrate synthase and cytochrome c oxidase, which have been used as constitutive mitochondrial enzymes (Freeman et al, 1986;Oberley et al, 1987;Vuorinen et al, 1995), did not differ significantly between the two cell lines.…”

Section: Mnsod Citrate Synthase and Cytochrome C Oxidasesupporting

confidence: 82%

“…Its pathogenesis has been postulated to be associated with the generation of free radicals (Kamp et al, 1992;Mossman et al, 1996). In contrast to previous observations, which have shown that MnSOD is usually low in malignant tumours (Oberley and Buettner, 1979;Oberley and Oberley, 1997), we have recently shown that the mRNA level, immunoreactive protein and specific activity of MnSOD are highly expressed in the tumour cells of malignant mesotheliomas when compared to healthy pleura or non-malignant transformed human mesothelial cells (Met5A) (Kinnula et al, 1996;Kahlos et al, 1998). Mesothelioma is resistant to cytotoxic drugs and radiation, both of which are known to induce generation of ROS (Sinha and Mimnaugh, 1990;Nakano et al, 1996).…”

contrasting

confidence: 49%

“…M38K cells were chosen because they contain the highest MnSOD activity of these cell lines and are extremely resistant to oxidant-induced cytotoxicity (Kinnula et al, 1996Kahlos et al, 1998). Transformed human pleural mesothelial cells (Met5A) were SV-40 virus transformed, immortalized, nontumorigenic and near-diploid cells (Ke et al, 1989), and were a gift from the National Cancer Institute, Bethesda, MD, USA (Dr CC Harris).…”

Section: Cell Culturementioning

confidence: 99%

“…Mesothelioma is resistant to cytotoxic drugs and radiation, both of which are known to induce generation of ROS (Sinha and Mimnaugh, 1990;Nakano et al, 1996). Accordingly, mesothelioma cell line cells are very resistant to a superoxide radicalproducing oxidant, menadione, and to epirubicin, which is an anthracycline often used in the treatment of mesothelioma (Kinnula et al, 1996;Kahlos et al, 1998).…”

mentioning

confidence: 99%

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Generation of reactive oxygen species by human mesothelioma cells

et al. 1999

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Malignant mesothelioma cells contain elevated levels of manganese superoxide dismutase (MnSOD) and are highly resistant to oxidants compared to non-malignant mesothelial cells. Since the level of cellular free radicals may be important for cell survival, we hypothesized that the increase of MnSOD in the mitochondria of mesothelioma cells may alter the free radical levels of these organelles. First, MnSOD activity was compared to the activities of two constitutive mitochondrial enzymes; MnSOD activity was 20 times higher in the mesothelioma cells than in the mesothelial cells, whereas the activities of citrate synthase and cytochrome c oxidase did not differ significantly in the two cell lines. This indicates that the activity of MnSOD per mitochondrion was increased in the mesothelioma cells. Superoxide production was assayed in the isolated mitochondria of these cells using lucigenin chemiluminescence. Mitochondrial superoxide levels were significantly lower (72%) in the mesothelioma cells compared to the mesothelial cells. Oxidant production in intact cells, assayed by fluorimetry using 2′,7′-dichlorodihydrofluorescein as a fluorescent probe, did not differ significantly between these cells. We conclude that mitochondrial superoxide levels are lower in mesothelioma cells compared to nonmalignant mesothelial cells, and that this difference may be explained by higher MnSOD activity in the mitochondria of these cells. Oxidant production was not different in these cells, which may be due to the previously observed increase in H 2 O 2 -scavenging mechanisms of mesothelioma cells. © 1999 Cancer Research Campaign

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Section: Mnsod Citrate Synthase and Cytochrome C Oxidasesupporting

confidence: 82%

contrasting

confidence: 49%

Section: Cell Culturementioning

confidence: 99%

mentioning

confidence: 99%

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Generation of reactive oxygen species by human mesothelioma cells

et al. 1999

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“…Asbestos fibres have been shown to cause up-regulation of MnSOD, an important mitochondrial superoxide radical-scavenging enzyme, in bronchial epithelial cells and mesothelial cells (Mossman et al, 1986;Janssen et al, 1994). We have previously shown that human mesothelioma cells contain high MnSOD levels and that these mesothelioma cells are more resistant than non-malignant mesothelial cells against the exogenous oxidant menadione (Kinnula et al, 1996). Because cytotoxic drugs generate both superoxide and hydrogen peroxide, it is likely that hydrogen peroxide-scavenging mechanisms are also involved in the observed resistance of this tumour against oxidant producing chemotherapeutic drugs.…”

mentioning

confidence: 99%

Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity

Kinnula

Linnainmaa²,

Ko³

et al. 1998

Br J Cancer

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Summary We have previously shown that cultured malignant mesothelioma cells contain elevated manganese superoxide dismutase (MnSOD) mRNA levels and activities compared with non-malignant mesothelial cells. As many cytotoxic drugs generate both superoxide and hydrogen peroxide, we assessed the relative significance of catalase and the glutathione redox cycle, as well as glutathione S-transferase (GST), in protecting these cells against hydrogen peroxide and epirubicin toxicity. Mesothelioma cell lines containing high (M38K cells) and low (M14K cells) MnSOD, and non-malignant MeT-5A mesothelial cells were selected for the study. M38K cells were the most resistant of these three cell types to hydrogen peroxide (0.1-0.5 mm, 4 h) and epirubicin (0.1-0.5,g ml-', 48 h) as judged by lactate dehydrogenase (LDH) release and by high-energy nucleotide (ATP, ADP, AMP) depletion. Total glutathione was higher in M38K cells (63.8 ± 20.3 nnmol mg-1 protein) than in M14K (25.2 ± 8.2 nmol mg-') or MeT-5A cells (23.5 ± 4.5 nmol mg-'). Furthermore, GST specific activity was higher in M38K cells (111.3 ± 15.8 U mg-') than in M14K cells (77.4 ± 6.6 U mg-') or in MeT-5A cells (68.8 ± 7.6 U mg-'). Western blotting indicated the presence of GST-i in all these cells, the reactivity again being highest in M38K cells. Depletion of glutathione by buthionine sulphoximine and inhibition of catalase by aminotriazole enhanced hydrogen peroxide toxicity in all cell types, while only the depletion of glutathione increased epirubicin toxicity. We conclude that simultaneous induction of multiple antioxidant enzymes can occur in human mesothelioma cells. In addition to the high MnSOD activity, hydrogen peroxide scavenging antioxidant enzymes, glutathione and GST can partly explain the high hydrogen peroxide and epirubicin resistance of these cells in vitro.

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