Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/806833

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Title
Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase
Author/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
Institution
The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
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.
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
Date
2009
Publisher
Elsevier
Keyword(s)
methylmercury;  glutathione peroxidase;  apoptosis;  mitochondria;  SH-SY5Y cells;  free radicals
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/806833
Identifier
ISSN:0891-5849
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Subject
"Free Radical Biology and Medicine"
 
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