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Mechanisms underlying striatal vulnerability to 3-nitropropionic acid.
J Neurochem. 2010 Jul; 114(2):597-605.JN

Abstract

The striatum is a cerebral structure particularly susceptible to the metabolic challenge exerted by 3-nitropropionic acid (3-NPA), a toxin that inhibits the respiratory chain at complex II. The striatum, which receives the nerve endings of the nigro-striatal pathway, concentrates the largest amount of 3,4-dihydroxyphenylethylamine or dopamine (DA) in the brain. DA is metabolized to 3,4-dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO), an enzyme that contains a redox-active disulfide in the active site. In striatum isolated nerve endings exposed to 3-NPA in vitro, DA increased and DOPAC decreased already after 10 min, and after 2 h also an increase in reactive oxygen species and DA-quinone products formation was detected. These 3-NPA-induced effects resulted in an increase in DA release after 2 h. In striatum homogenates from animals presenting motor disturbances in response to 3-NPA in vivo, the DA metabolites homovanillic acid and DOPAC were increased. It is concluded that in the striatum nerve endings where DA is particularly concentrated, the increase in reactive oxygen species induced by 3-NPA, oxidizes DA generating DA-quinones. These DA-quinones may form adducts with the active site of MAO type A reducing its activity. The DA not metabolized to DOPAC is both, used to unchain generation of more of the harmful DA-oxidation products and released to the external medium, where is metabolized by the non-neuronal enzymes MAO type B and catechol-O-methyltransferase.

Authors+Show Affiliations

Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México DF, México.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20477912

Citation

Herrera-Mundo, Nieves, and María Sitges. "Mechanisms Underlying Striatal Vulnerability to 3-nitropropionic Acid." Journal of Neurochemistry, vol. 114, no. 2, 2010, pp. 597-605.
Herrera-Mundo N, Sitges M. Mechanisms underlying striatal vulnerability to 3-nitropropionic acid. J Neurochem. 2010;114(2):597-605.
Herrera-Mundo, N., & Sitges, M. (2010). Mechanisms underlying striatal vulnerability to 3-nitropropionic acid. Journal of Neurochemistry, 114(2), 597-605. https://doi.org/10.1111/j.1471-4159.2010.06789.x
Herrera-Mundo N, Sitges M. Mechanisms Underlying Striatal Vulnerability to 3-nitropropionic Acid. J Neurochem. 2010;114(2):597-605. PubMed PMID: 20477912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms underlying striatal vulnerability to 3-nitropropionic acid. AU - Herrera-Mundo,Nieves, AU - Sitges,María, Y1 - 2010/04/30/ PY - 2010/5/19/entrez PY - 2010/5/19/pubmed PY - 2010/8/24/medline SP - 597 EP - 605 JF - Journal of neurochemistry JO - J Neurochem VL - 114 IS - 2 N2 - The striatum is a cerebral structure particularly susceptible to the metabolic challenge exerted by 3-nitropropionic acid (3-NPA), a toxin that inhibits the respiratory chain at complex II. The striatum, which receives the nerve endings of the nigro-striatal pathway, concentrates the largest amount of 3,4-dihydroxyphenylethylamine or dopamine (DA) in the brain. DA is metabolized to 3,4-dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO), an enzyme that contains a redox-active disulfide in the active site. In striatum isolated nerve endings exposed to 3-NPA in vitro, DA increased and DOPAC decreased already after 10 min, and after 2 h also an increase in reactive oxygen species and DA-quinone products formation was detected. These 3-NPA-induced effects resulted in an increase in DA release after 2 h. In striatum homogenates from animals presenting motor disturbances in response to 3-NPA in vivo, the DA metabolites homovanillic acid and DOPAC were increased. It is concluded that in the striatum nerve endings where DA is particularly concentrated, the increase in reactive oxygen species induced by 3-NPA, oxidizes DA generating DA-quinones. These DA-quinones may form adducts with the active site of MAO type A reducing its activity. The DA not metabolized to DOPAC is both, used to unchain generation of more of the harmful DA-oxidation products and released to the external medium, where is metabolized by the non-neuronal enzymes MAO type B and catechol-O-methyltransferase. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/20477912/Mechanisms_underlying_striatal_vulnerability_to_3_nitropropionic_acid_ L2 - https://doi.org/10.1111/j.1471-4159.2010.06789.x DB - PRIME DP - Unbound Medicine ER -