Reduced levels of catalase activity potentiate MPP+-induced toxicity: comparison between MN9D cells and CHO cells

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to be to xic by inducing oxygen free radicals in the mammalian nervous system, espec ially in the nigrostriatal dopaminergic system. The present study was desig ned to compare the toxic effects of MPP+, the active metabolite of MPTP, in MN9D neuronal cells that exhibit relatively low levels of catalase activit y, as compared to CHO cells, which exhibit high levels of catalase activity . The survival of the MN9D cells in the presence of 250 mu M MPP+ was less than 10%, whereas CHO cells exhibited 70% survival at the same concentratio n of MPP+. The ED50 values of MPP+ in MN9D and CHO cell lines were 60-600 m u M, respectively. MN9D cells contain less catalase, an enzyme believed to be involved in the detoxification of free radicals compared to CHO cells. T he catalase activity was 2 Units/mg protein in MN9D cells and 30 U/mg prote in in CHO cells. The catalase activity in CHO cells increased with increasi ng MPP+ concentrations from 100-500 mu M, however, it decreased at 1 mM MPP +. In contrast, catalase activity in MN9D remained the same at all MPP+ con centrations. When the CHO cells were pre-treated with 10-25 mM 3-aminotriaz ole (3-AT), which inhibits catalase activity, and exposed to MPP+ at variou s concentrations, they became susceptible to MPP+. It is evident from these data that the differential susceptibility to MPP+ in these two cell lines are due to differences in catalase activity. In addition, the inhibition of constituentive catalase activity in CHO cells by 3-AT treatment enhances t heir susceptibility. In conclusion, the study demonstrates that catalase ac tivity represents an important defence mechanism in MPTP-induced toxicity. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.