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Manganese and 1-methyl-4-(2′-ethylphenyl)-1,2,3,6-tetrahydropyridine induce apoptosis in PC12 cells

Desole, Maria Speranza and Sciola, Gian Luigi and Delogu, Maria Rosaria and Sircana, Sara and Migheli, Rossana (1996) Manganese and 1-methyl-4-(2′-ethylphenyl)-1,2,3,6-tetrahydropyridine induce apoptosis in PC12 cells. Neuroscience Letters, Vol. 209 (3), p. 193-196. ISSN 0304-3940. Article.

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DOI: 10.1016/0304-3940(96)12645-8

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′-deoxyuridine-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.

Item Type:Article
ID Code:4187
Status:Published
Refereed:Yes
Uncontrolled Keywords:Manganese, 1-Methyl-4-(2′-ethylphenyl)-1,2,3,6-tetrahydropyridine (2′Et-MPTP), oxidative stress, apoptosis, PC12 cells
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Area 05 - Scienze biologiche > BIO/06 Anatomia comparata e citologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze fisiologiche, biochimiche e cellulari
001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
Publisher:Elsevier Science Ireland
ISSN:0304-3940
Deposited On:15 Jul 2010 12:26

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