Does thioredoxin-1 prevent mitochondria- and endoplasmic reticulum-mediated neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine?
Antioxid Redox Signal
; 9(5): 603-8, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17465883
ABSTRACT
We show that 1-methyl-4-phenylpyridinium ion (MPP(+)), an active metabolite of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), induces cytotoxicity via endoplasmic reticulum (ER)- and mitochondria-mediated pathways, and thioredoxin-1 (TRX-1), a redox-active protein, prevents MPTP-induced neurotoxicity. TRX-1 overexpression suppressed reactive oxygen species and the ATP decline caused by MPP(+) in HepG2 cells. MPP(+) activated caspase-12 in PC12 cells and induced cytotoxicity in HeLa-rho(0) cells lacking mitochondrial DNA, as well as in the parental HeLa-S3 cells. TRX-1-transgenic mice demonstrated significant resistance to caspase-12 activation and the apoptotic decrease of dopaminergic neurons after MPTP administration, compared with wild-type C57BL/6 mice.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiorredoxinas
/
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina
/
Retículo Endoplasmático
/
Mitocôndrias
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Antioxid Redox Signal
Assunto da revista:
METABOLISMO
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão