Dysfunction of mitochondrial Lon protease and identification of oxidized protein in mouse brain following exposure to MPTP: Implications for Parkinson disease.
Free Radic Biol Med
; 108: 236-246, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28365360
ABSTRACT
Compelling evidence suggests that mitochondrial dysfunction leading to reactive oxygen species (ROS) production and protein oxidation could represent a critical event in the pathogenesis of Parkinson's disease (PD). Pioneering studies have shown that the mitochondrial matrix contains the Lon protease, which degrades oxidized, dysfunctional, and misfolded protein. Using the PD animal model of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication in mice, we showed that Lon protease expression increased in the ventral mesencephalon of intoxicated animals, concomitantly with the appearance of oxidized proteins and dopaminergic cell loss. In addition, we report that Lon is inactivated by ROS. Moreover, proteomic experiments provide evidence of carbonylation in α-ketoglutarate dehydrogenase (KGDH), aconitase or subunits of respiratory chain complexes. Lon protease inactivation upon MPTP treatment in mice raises the possibility that Lon protease dysfunction is an early event in the pathogenesis of PD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Mesencéfalo
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Protease La
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Neurônios Dopaminérgicos
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Mitocôndrias
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Free Radic Biol Med
Assunto da revista:
BIOQUIMICA
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MEDICINA
Ano de publicação:
2017
Tipo de documento:
Article