Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.6/3937
Título: Antioxidant enzymes and their role in paraquat induced dopaminergic toxicity
Outros títulos: Enzimas antioxidantes e o seu papel na toxicidade dopaminergica induzido pelo paraquat: contribution of NADPH oxidase 1 da NADPH oxidase 1
Autor: Morais, Ana Francisca da Silva
Orientador: Baltazar, Graça Maria Fernandes
Cristóvão, Ana Clara
Palavras-chave: Doença de Parkinson
Doença de Parkinson - Pesticida - Paraquato
Superoxido dismutase
Enzimas antioxidantes
NADPH oxidase (Nox)
Data de Defesa: 2010
Resumo: Parkinson´s Disease (PD) is a chronic progressive neurodegenerative disease; characterized by degeneration of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several environmental conditions such as exposure to pesticides like Paraquat (PQ) are considered risk factors for PD. Treatment of animal models with PQ induces changes characteristic of parkinsonism. The cellular toxicity of PQ is, in part, due to its redox cycle of reactions that lead to the generation of reactive oxygen species (ROS), mainly hydrogen peroxide, and hydroxyl radical and to the consequent cellular damage. To cope with the many oxidative reactions, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and gluthathione peroxidise are present in cells to balance the oxidative mechanisms Therefore, in order to counteract the oxidative stress, ROS inducers can also trigger an increase of antioxidant enzymes levels. PQ induces its toxic effects on N27 cells by activating the NADPH oxidase (Nox) system, particularly Nox1, which, in turn, generates ROS. Taking in account this data we raise the possibility that dopaminergic Nox1 may be involved in the regulating the expression of antioxidant enzymes. We assessed mRNA levels of SOD and CAT after 1 and 6h exposure to PQ in N27 cells. Protein levels were evaluated after an incubation with PQ during 16 and 24h, with or without the presence of apocynin, an inhibitor of Nox. We also studied SOD and CAT protein levels in the SN of rats exposed to PQ. Stimulation of N27 cells with low concentrations of PQ increased SOD mRNA expression levels, whereas increases of CAT mRNA levels were observed in cells exposed to high concentrations of PQ for 1h. . However, CAT protein levels were increased by incubation, for 24hr, with 1000 μM PQ, and SOD levels were increased by incubation with low concentration of PQ. The increase of both SOD and CAT protein levels induced by PQ was reduced by the in vivo Nox1 silencing, results concordant with the the immunohistochemistry data. In conclusion, with the present study, we demonstrated that PQ increases SOD and CAT expression and that Nox1 may be involved in the regulation of these antioxidant enzymes.
URI: http://hdl.handle.net/10400.6/3937
Designação: Mestrado em Bioquímica
Aparece nas colecções:FC - DQ | Dissertações de Mestrado e Teses de Doutoramento

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