Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase.
 

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05-20-09 09:56 AM
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Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase.
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Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase.

Free Radic Biol Med. 2009 May 15;

Authors: Franco JL, Posser T, Dunkley PR, Dickson PW, Mattos JJ, Martins R, Bainy AC, Marques MR, Dafre AL, Farina M

In the present study, we investigated the involvement of glutathione peroxidase - GPx (EC 1.11.1.9) on methylmercury (MeHg)-induced toxicity using three different 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; 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 (PARP) cleavage, an index of apoptosis. Second, in mitochondrial-enriched fractions isolated from MeHg-treated mice, there was a significant reduction of 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 hours with MeHg showed a significant reduction of 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.

PMID: 19450679 [PubMed - as supplied by publisher]