- Title
- Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase
- Creator
- Franco, Jeferson L.; Posser, Thaís; Dunkley, Peter R.; Dickson, Phillip W.; Mattos, Jacó J.; Martins, Roberta; Bainy, Afonso C. D.; Marques, Maria R.; Dafre, Alcir L.; Farina, Marcelo
- Relation
- Free Radical Biology and Medicine Vol. 47, Issue 4, p. 449-457
- Publisher Link
- http://dx.doi.org/10.1016/j.freeradbiomed.2009.05.013
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2009
- Description
- In this study, we investigated the involvement of glutathione peroxidase—GPx in methylmercury (MeHg)-induced toxicity using three models: (a) in mouse brain after treatment with MeHg (40 mg/L in drinking water), (b) in mouse brain mitochondrial-enriched fractions isolated from MeHg-treated animals, and (c) in cultured human neuroblastoma SH-SY5Y cells. First, adult male Swiss mice exposed to MeHg for 21 days showed a significant decrease in GPx activity in the brain and an increase in poly(ADP-ribose) polymerase cleavage, an index of apoptosis. Second, in mitochondrial-enriched fractions isolated from MeHg-treated mice, there was a significant reduction in GPx activity and a concomitant decrease in mitochondrial activity and increases in ROS formation and lipid peroxidation. Incubation of mitochondrial-enriched fractions with mercaptosuccinic acid, a GPx inhibitor, significantly augmented the toxic effects of MeHg administered in vivo. Incubation of mitochondrial-enriched fractions with exogenous GPx completely blocked MeHg-induced mitochondrial lipid peroxidation. Third, SH-SY5Y cells treated for 24 h with MeHg showed a significant reduction in GPx activity. There was a concomitant significant decrease in cell viability and increase in apoptosis. Inhibition of GPx substantially enhanced MeHg toxicity in the SH-SY5Y cells. These results suggest that GPx is an important target for MeHg-induced neurotoxicity, presumably because this enzyme is essential for counteracting the pro-oxidative effects of MeHg both in vitro and in vivo.
- Subject
- methylmercury; glutathione peroxidase; apoptosis; mitochondria; SH-SY5Y cells; free radicals
- Identifier
- uon:7232
- Identifier
- http://hdl.handle.net/1959.13/806833
- Identifier
- ISSN:0891-5849
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