NMDA-receptors are involved in Cu2+/paraquat-induced death of cultured cerebellar granule neurons
- 61 Downloads
Rat cultured cerebellar granule neurons (CGNs) were not sensitive to CuCl2 (1-10 µM, 24 h), whereas paraquat (150 µM) decreased neuronal survival to 79 ± 3% of control level. Simultaneous treatment of CGNs with paraquat and CuCl2 (2, 5, or 10 µM Cu2+/paraquat) caused significant copper dose-dependent death, lowering their survival to 56 ± 4, 37 ± 3, or 16 ± 2%, respectively, and stimulating elevated production of free radicals in CGNs. Introduction of vitamin E, a non-competitive antagonist of NMDA subtype of glutamate receptors (MK-801), and also removal of glutamine from the incubation medium decreased toxicity of Cu2+/paraquat mixture. However, addition of Cu2+ into the incubation medium did not affect CGNs death caused by glutamate. These data emphasize that excessive copper in the brain may trigger oxidative stress, which in turn results in release of glutamate, overstimulation of glutamate receptors, and neuronal death.
Keywordscopper paraquat cerebellar granule neurons free radicals glutamate
Unable to display preview. Download preview PDF.
- 13.Cristovao, A. C., Choi, D. H., Baltazar, G., Beal, M. F., and Kim, Y. S. (2009) The role of NADPH oxidase 1derived reactive oxygen species in paraquat-mediated dopaminergic cell death, Antioxid. Redox Signal., 11, 2105-2018.Google Scholar
- 14.Stelmashook, E. V., Isaev, N. K., Plotnikov, E. Y., Uzbekov, R. E., Alieva, I. B., Arbeille, B., and Zorov, D. B. (2009) Effect of transitory glucose deprivation on mitochondrial structure and functions in cultured cerebellar granule neurons, Neurosci. Lett., 461, 140–144.CrossRefPubMedGoogle Scholar
- 19.Samuele, A., Mangiagalli, A., Armentero, M. T., Fancellu, R., Bazzini, E., Vairetti, M., Ferrigno, A., Richelmi, P., Nappi, G., and Blandini, F. (2005) Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson’s disease, Biochim. Biophys. Acta, 1741, 325–330.CrossRefPubMedGoogle Scholar
- 23.Rodriguez-Rocha, H., Garcia-Garcia, A., Pickett, C., Li, S., Jones, J., Chen, H., Webb, B., Choi, J., Zhou, Y., Zimmerman, M. C., and Franco, R. (2013) Compartmentalized oxidative stress in dopaminergic cell death induced by pesticides and complex I inhibitors: distinct roles of superoxide anion and superoxide dismutases, Free Radic. Biol. Med., 61, 370–383.CrossRefPubMedGoogle Scholar