Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.

Mitochondrial dysfunction and oxidative stress are considered central in dopaminergic neurodegeneration in Parkinson's disease (PD). Oxidative stress occurs when the endogenous antioxidant systems are overcome by the generation of reactive oxygen species (ROS). A plausible source of oxidative s...

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Autores principales:	Elisa Belluzzi, Marco Bisaglia, Elisabetta Lazzarini, Leandro C Tabares, Mariano Beltramini, Luigi Bubacco
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/46ba7522bf0c4655a3a39b4383c4e229
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spelling	oai:doaj.org-article:46ba7522bf0c4655a3a39b4383c4e2292021-11-18T07:15:15ZHuman SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.1932-620310.1371/journal.pone.0038026https://doaj.org/article/46ba7522bf0c4655a3a39b4383c4e2292012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22723845/?tool=EBIhttps://doaj.org/toc/1932-6203Mitochondrial dysfunction and oxidative stress are considered central in dopaminergic neurodegeneration in Parkinson's disease (PD). Oxidative stress occurs when the endogenous antioxidant systems are overcome by the generation of reactive oxygen species (ROS). A plausible source of oxidative stress, which could account for the selective degeneration of dopaminergic neurons, is the redox chemistry of dopamine (DA) and leads to the formation of ROS and reactive dopamine-quinones (DAQs). Superoxide dismutase 2 (SOD2) is a mitochondrial enzyme that converts superoxide radicals to molecular oxygen and hydrogen peroxide, providing a first line of defense against ROS. We investigated the possible interplay between DA and SOD2 in the pathogenesis of PD using enzymatic essays, site-specific mutagenesis, and optical and high-field-cw-EPR spectroscopies. Using radioactive DA, we demonstrated that SOD2 is a target of DAQs. Exposure to micromolar DAQ concentrations induces a loss of up to 50% of SOD2 enzymatic activity in a dose-dependent manner, which is correlated to the concomitant formation of protein aggregates, while the coordination geometry of the active site appears unaffected by DAQ modifications. Our findings support a model in which DAQ-mediated SOD2 inactivation increases mitochondrial ROS production, suggesting a link between oxidative stress and mitochondrial dysfunction.Elisa BelluzziMarco BisagliaElisabetta LazzariniLeandro C TabaresMariano BeltraminiLuigi BubaccoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e38026 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisa Belluzzi Marco Bisaglia Elisabetta Lazzarini Leandro C Tabares Mariano Beltramini Luigi Bubacco Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.
description	Mitochondrial dysfunction and oxidative stress are considered central in dopaminergic neurodegeneration in Parkinson's disease (PD). Oxidative stress occurs when the endogenous antioxidant systems are overcome by the generation of reactive oxygen species (ROS). A plausible source of oxidative stress, which could account for the selective degeneration of dopaminergic neurons, is the redox chemistry of dopamine (DA) and leads to the formation of ROS and reactive dopamine-quinones (DAQs). Superoxide dismutase 2 (SOD2) is a mitochondrial enzyme that converts superoxide radicals to molecular oxygen and hydrogen peroxide, providing a first line of defense against ROS. We investigated the possible interplay between DA and SOD2 in the pathogenesis of PD using enzymatic essays, site-specific mutagenesis, and optical and high-field-cw-EPR spectroscopies. Using radioactive DA, we demonstrated that SOD2 is a target of DAQs. Exposure to micromolar DAQ concentrations induces a loss of up to 50% of SOD2 enzymatic activity in a dose-dependent manner, which is correlated to the concomitant formation of protein aggregates, while the coordination geometry of the active site appears unaffected by DAQ modifications. Our findings support a model in which DAQ-mediated SOD2 inactivation increases mitochondrial ROS production, suggesting a link between oxidative stress and mitochondrial dysfunction.
format	article
author	Elisa Belluzzi Marco Bisaglia Elisabetta Lazzarini Leandro C Tabares Mariano Beltramini Luigi Bubacco
author_facet	Elisa Belluzzi Marco Bisaglia Elisabetta Lazzarini Leandro C Tabares Mariano Beltramini Luigi Bubacco
author_sort	Elisa Belluzzi
title	Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.
title_short	Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.
title_full	Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.
title_fullStr	Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.
title_full_unstemmed	Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.
title_sort	human sod2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for parkinson's disease.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/46ba7522bf0c4655a3a39b4383c4e229
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Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease.

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