Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis.
Biochem Biophys Res Commun
; 457(1): 95-100, 2015 Jan 30.
Article
en En
| MEDLINE
| ID: mdl-25545062
ABSTRACT
Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson's disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson's disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Paraquat
/
Ácidos Docosahexaenoicos
/
Especies Reactivas de Oxígeno
/
Neuronas Dopaminérgicas
/
Glutatión
/
Homeostasis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2015
Tipo del documento:
Article