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KMID : 0371019990320040459
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Journal of Preventive Medicine and Public Health
1999 Volume.32 No. 4 p.459 ~ p.466
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Nitric Oxide-Mediated Cytotoxicity of Manganese in Basal Ganglia Neutronal Cells
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Shin Dong-Hoon
Jung Yong-Wook
Bae Jae-Hoon
Song Dae-Kyu
Park Won-Kyun
Ko Bok-Hyun
Kim Doo-Hee
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Abstract
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Objectives : We have investigated to manifest whether manganese-induced neurotoxicity is mediated by nitric oxide(NO) in the rat primary neuronal cultures and assess the effect of Mn2+ on the N-methyl-D aspartate(NMDA) receptors.
Methods : We have used 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay to examine the effect of cytotoxicity of MnCl2 in neuronal cells. NO production was determined by measuring nirites, a stable oxidation product of NO. The neurons in the rat that contains neuronal nitric oxide synthase(nNOS) were examined by immunofluorescence and confocal microscopy. The effects of Mn2+ on the NMDA receptors was assessed by the whole cell voltage clamp technique.
Results : We showed that the NO release and NOS expression were increased with 500uM MnCl2 treatment and an NOS inhibitors, NG-nitro-L-arginine, prevented neurotoxicity elicited by manganese. In the electophysiological study, Mn2+ does not block or activate the NMDA receptors and not pass through the NMDA receptors in a neurons of basal ganglia.
Conclusions : It is concluded that manganese neurotoxicity in basal ganglia was partially mediated by nitric oxide in the cell culture model.
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KEYWORD
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Manganese, Mn, Nitric oxide, NO, Nitric oxide synthase, NOS, Neurotoxicity, Neurons
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