Role of oxidative stress in the manganese and 1-methyl-4-(2′-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced apoptosis in PC12 cells

Role of oxidative stress in the manganese and... Oxidative stress is thought to play a key role in the apoptotic death of several cellular systems, including neurons. Oxidative stress is proposed also as a mechanism of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and manganese (Mn)-induced neuronal death. We have recently shown 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, induce apoptosis in PC12 cells. In the present study, we evaluated the effects of deprenyl and the antioxidant drugs N -acetylcysteine (NAC) and ascorbic acid (AA) on Mn- and 2′Et-MPTP-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. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mn-induced apoptosis and decrease in cell viability was inhibited by the antioxidants NAC and AA. Deprenyl failed to inhibit the above Mn effects. Neither NAC, AA nor deprenyl were able to inhibit both 2′Et-MPTP-induced apoptosis and decrease in cell viability. These results confirm that apoptosis may be an important mechanism of cell death in MPTP- and Mn-induced parkinsonism. However, an oxidative stress mechanism may be recognized, at least in vitro , only in the Mn-induced apoptosis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurochemistry International Elsevier

Role of oxidative stress in the manganese and 1-methyl-4-(2′-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced apoptosis in PC12 cells

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Publisher
Elsevier
Copyright
Copyright © 1997 Elsevier Science Ltd
ISSN
0197-0186
D.O.I.
10.1016/S0197-0186(96)00146-5
Publisher site
See Article on Publisher Site

Abstract

Oxidative stress is thought to play a key role in the apoptotic death of several cellular systems, including neurons. Oxidative stress is proposed also as a mechanism of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and manganese (Mn)-induced neuronal death. We have recently shown 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, induce apoptosis in PC12 cells. In the present study, we evaluated the effects of deprenyl and the antioxidant drugs N -acetylcysteine (NAC) and ascorbic acid (AA) on Mn- and 2′Et-MPTP-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. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Mn-induced apoptosis and decrease in cell viability was inhibited by the antioxidants NAC and AA. Deprenyl failed to inhibit the above Mn effects. Neither NAC, AA nor deprenyl were able to inhibit both 2′Et-MPTP-induced apoptosis and decrease in cell viability. These results confirm that apoptosis may be an important mechanism of cell death in MPTP- and Mn-induced parkinsonism. However, an oxidative stress mechanism may be recognized, at least in vitro , only in the Mn-induced apoptosis.

Journal

Neurochemistry InternationalElsevier

Published: Jun 7, 1997

References

  • Allopurinol protects against manganese-induced oxidative stress in the striatum and in the brainstem of the rat
    Desole, M.S; Esposito, G; Migheli, R; Fresu, L; Sircana, S; Miele, M; De Natale, G; Miele, E
  • Identification of programmed cell death in situ via specific labelling of nuclear DNA fragmentation
    Gavrieli, Y; Sherman, Y; Ben-Sasson, S.A
  • Oxidative stress induces apoptosis in embryonic cortical neurons
    Ratan, R.R; Murphy, T.H; Baraban, J.M
  • Rescue of dying neurons: a new action for deprenyl in MPTP parkinsonism
    Tatton, W.G; Greenwood, C.E

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