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  • Title: Manganese and 1-methyl-4-(2'-ethylpheny1)-1,2,3,6-tetrahydropyridine induce apoptosis in PC12 cells.
    Author: Desole MS, Sciola L, Delogu MR, Sircana S, Migheli R.
    Journal: Neurosci Lett; 1996 May 17; 209(3):193-6. PubMed ID: 8736643.
    Abstract:
    Oxidative stress is thought to play a key role both in the neurotoxin MPTP- and manganese (Mn)-induced neurotoxicity and in apoptotic cell death. In the present study, we report that Mn and the MPTP analogue 1-methyl-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 (at concentrations of 0.5 and 1.0 mM), induced apoptosis in PC12 cells. Apoptosis was tested by terminal deoxynucleotidyl transferase-mediated 2'-deoxy-uridine-5'-triphosphate nick end labelling (TUNEL) technique, flow cytometry and fluorescence microscopy. Both Mn and 2'Et-MPTP induced also a time-dependent decrease in cell viability, as determined by the 3-(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 parkinsonism. However, an oxidative stress mechanism may be recognized only in the Mn-induced apoptosis.
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