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Korean Journal of Preventive Medicine 1999;32(4): 459-466.
Nitric Oxide-Mediated Cytotoxicity of Manganese in Basal Ganglia Neuronal Cells.
Dong Hoon Shin, Yong Wook Jung, Jae Hoon Bae, Dae Kyu Song, Won Kyun Park, Bok Hyun Ko, Doo Hie Kim
1Department of Preventive Medicine, School of Medicine, Keimyung University, Korea.
2Department of Physiology, School of Medicine, Keimyung University, Korea.
3Department of Anatomy, School of Medicine, Dongguk University, Korea.
4Preventive Medicine, School of Medicine, Dongguk University, Korea.
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 assesed 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 electrophysiological 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.
Key words: Manganese(Mn); Nitric oxide(NO); Nitric oxide synthase(NOS); Neurotoxicity; Neurons
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