DJ-1 mediates paraquat-induced dopaminergic neuronal cell death.
Toxicol Lett
; 202(2): 85-92, 2011 Apr 25.
Article
en En
| MEDLINE
| ID: mdl-21300143
ABSTRACT
There are two causes of Parkinson's disease (PD) environmental insults and genetic mutations of PD-associated genes. Environmental insults and genetic mutations lead to mitochondrial dysfunction, and a combination of mitochondrial dysfunction and increased oxidative stress in dopaminergic neurons is thought to contribute to the pathogenesis of PD. Among the PD-associated genes, DJ-1 acts as a redox sensor for oxidative stress and has been also proposed to maintain mitochondrial complex I activity. To understand molecular functions of DJ-1 in the cell, we have generated DJ-1 null cells from the DJ-1(-/-) mouse embryos. Using these null cells, we investigated the susceptibility to an environmental toxin, paraquat, which is known to inhibit mitochondrial complex I. Interestingly, we found that DJ-1 null cells showed a resistance to paraquat-induced apoptosis, including reduced poly (ADP-ribose) polymerase and procaspase-3. Also DJ-1 null cells generated less superoxide than SN4741 cells by paraquat treatment. Consistent with the reduced paraquat sensitivity, DJ-1 null cells showed reduced complex I activity, which was partially rescued by ectopic DJ-I expression. In summary, our results suggest that DJ-1 is critical to maintain mitochondrial complex I and complex I could be a key target in interaction of paraquat toxicity and DJ-1 for giving rise to PD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Paraquat
/
Enfermedad de Parkinson
/
Dopamina
/
Apoptosis
/
Proteínas Oncogénicas
/
Estrés Oxidativo
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Año:
2011
Tipo del documento:
Article
País de afiliación:
Corea del Sur