Manganese and 1-methyl-4-(2'-ethylpheny1)-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 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.
Desole
M S
MS
Institute of Pharmacology, University of Sassari, Italy. desole@ssmain.uniss.it
Sciola
L
L
Delogu
M R
MR
Sircana
S
S
Migheli
R
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005821:Genetic Techniques; D008345:Manganese / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D014544:Uridine Triphosphate / Q000235:genetics / Q000378:metabolism
D008345:Manganese; D001205:Ascorbic Acid; D014544:Uridine Triphosphate