The neurotoxin MPTP does not affect striatal superoxide dismutase activity in mice

Eli Pikarsky; Eldad Melamed; Jutta Rosenthal; Anat Uzzan; Shalom D. Michowiz

doi:10.1016/0304-3940(87)90277-1

The neurotoxin MPTP does not affect striatal superoxide dismutase activity in mice

Eli Pikarsky, Eldad Melamed^*, Jutta Rosenthal, Anat Uzzan, Shalom D. Michowiz

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Intraneuronal superoxide generation may be a possible mechanism of the dopaminergic (DA) neurotoxicity of MPTP. In such case, MPTP might theoretically affect superoxide dismutase (SOD) activity. We determined SOD activity and DA levels in striata of mice at 0.5, 1, 4, 16, 24 h or 7 days after an acute single injection of MPTP (40 mg/kg, s.c.). MPTP produced marked striatal DA depletions from 4 h post-treatment but SOD activity remained unaltered and similar to controls at all time points. Intrastriatal injections of purified SOD 15 min prior to systemic administration of MPTP did not attenuate the MPTP-induced striatal DA depletions in mice at 7 days post-treatment. Combined administration of MPTP with the SOD inhibitor diethyldithiocarbamate markedly enhanced striatal DA decreases produced by MPTP alone. Findings suggest that MPTP does not act via inhibition of SOD. Therefore, potentiation of MPTP toxicity by diethyldithiocarbamate may be due to interference with other enzymatic systems.

Original language	English
Pages (from-to)	327-331
Number of pages	5
Journal	Neuroscience Letters
Volume	82
Issue number	3
DOIs	https://doi.org/10.1016/0304-3940(87)90277-1
State	Published - 4 Dec 1987
Externally published	Yes

Bibliographical note

Funding Information:
Supported, in part, by the American Parkinson's Disease Association, by the Karen and Erich Segal Foundation and by the Jacob and Hilda Blaustein Foundation, Inc.

Keywords

(MPTP)
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine
Diethyldithiocarbamate
Dopamine
Free radical
Nigrostriatal neuron
Superoxide dismutase

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title = "The neurotoxin MPTP does not affect striatal superoxide dismutase activity in mice",

abstract = "Intraneuronal superoxide generation may be a possible mechanism of the dopaminergic (DA) neurotoxicity of MPTP. In such case, MPTP might theoretically affect superoxide dismutase (SOD) activity. We determined SOD activity and DA levels in striata of mice at 0.5, 1, 4, 16, 24 h or 7 days after an acute single injection of MPTP (40 mg/kg, s.c.). MPTP produced marked striatal DA depletions from 4 h post-treatment but SOD activity remained unaltered and similar to controls at all time points. Intrastriatal injections of purified SOD 15 min prior to systemic administration of MPTP did not attenuate the MPTP-induced striatal DA depletions in mice at 7 days post-treatment. Combined administration of MPTP with the SOD inhibitor diethyldithiocarbamate markedly enhanced striatal DA decreases produced by MPTP alone. Findings suggest that MPTP does not act via inhibition of SOD. Therefore, potentiation of MPTP toxicity by diethyldithiocarbamate may be due to interference with other enzymatic systems.",

keywords = "(MPTP), 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine, Diethyldithiocarbamate, Dopamine, Free radical, Nigrostriatal neuron, Superoxide dismutase",

author = "Eli Pikarsky and Eldad Melamed and Jutta Rosenthal and Anat Uzzan and Michowiz, {Shalom D.}",

note = "Funding Information: Supported, in part, by the American Parkinson's Disease Association, by the Karen and Erich Segal Foundation and by the Jacob and Hilda Blaustein Foundation, Inc.",

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AU - Melamed, Eldad

AU - Rosenthal, Jutta

AU - Uzzan, Anat

AU - Michowiz, Shalom D.

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N2 - Intraneuronal superoxide generation may be a possible mechanism of the dopaminergic (DA) neurotoxicity of MPTP. In such case, MPTP might theoretically affect superoxide dismutase (SOD) activity. We determined SOD activity and DA levels in striata of mice at 0.5, 1, 4, 16, 24 h or 7 days after an acute single injection of MPTP (40 mg/kg, s.c.). MPTP produced marked striatal DA depletions from 4 h post-treatment but SOD activity remained unaltered and similar to controls at all time points. Intrastriatal injections of purified SOD 15 min prior to systemic administration of MPTP did not attenuate the MPTP-induced striatal DA depletions in mice at 7 days post-treatment. Combined administration of MPTP with the SOD inhibitor diethyldithiocarbamate markedly enhanced striatal DA decreases produced by MPTP alone. Findings suggest that MPTP does not act via inhibition of SOD. Therefore, potentiation of MPTP toxicity by diethyldithiocarbamate may be due to interference with other enzymatic systems.

AB - Intraneuronal superoxide generation may be a possible mechanism of the dopaminergic (DA) neurotoxicity of MPTP. In such case, MPTP might theoretically affect superoxide dismutase (SOD) activity. We determined SOD activity and DA levels in striata of mice at 0.5, 1, 4, 16, 24 h or 7 days after an acute single injection of MPTP (40 mg/kg, s.c.). MPTP produced marked striatal DA depletions from 4 h post-treatment but SOD activity remained unaltered and similar to controls at all time points. Intrastriatal injections of purified SOD 15 min prior to systemic administration of MPTP did not attenuate the MPTP-induced striatal DA depletions in mice at 7 days post-treatment. Combined administration of MPTP with the SOD inhibitor diethyldithiocarbamate markedly enhanced striatal DA decreases produced by MPTP alone. Findings suggest that MPTP does not act via inhibition of SOD. Therefore, potentiation of MPTP toxicity by diethyldithiocarbamate may be due to interference with other enzymatic systems.

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KW - 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine

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The neurotoxin MPTP does not affect striatal superoxide dismutase activity in mice

Abstract

Bibliographical note

Keywords

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