MANGANESE AND THYL-4-(2'-ETHYLPHENYL)-1,2,3,6-TETRAHYDROPYRIDINE INDUCE APOPTOSIS IN PC12 CELLS

Oxidative stress is thought to play a key role both in the neurotoxin MPTP- and manganese (Mn)-induced neurotoxicity and in apoptotic cell d eath. In the present study, we report that Mn and the MPTP analogue th yl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine (2'Et-MPTP), which is metabolized by MAO-A to 1-methyl-4-(2'-ethylphenyl)-pyridinium ion (a t concentrations of 0.5 and 1.0 mM), induced apoptosis in PC12 cells. Apoptosis was tested by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine-5'-triphosphate nick end labelling (TUNEL) technique, flow cytometry and fluorescence microscopy. Both Mn and 2'Et-MPTP ind uced also a time-dependent decrease in cell viability, as determined b y the (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Only Mn-induced apoptosis and decrease in cell viability were inhibited by the antioxidant ascorbic acid. We conclude that apoptosis may be an important mechanism of cell death in MPTP- and Mn-induced p arkinsonism. However, an oxidative stress mechanism may be recognized only in the Mn-induced apoptosis.