de Melo Reis Ricardo Augusto, Herculano Anderson Manoel, da Silva Maurício Castro Cabral, dos Santos Ronald Marques, do Nascimento José Luis Martins
Laboratory Neurochemistry, Program in Neurobiology IBCCF, UFRJ, Rio de Janeiro, Brazil.
Neurosci Res. 2007 Jul;58(3):278-84. doi: 10.1016/j.neures.2007.03.010. Epub 2007 Mar 31.
Methylmercury (MeHg) is related to several deleterious effects on the vertebrate nervous system and part of these effects are through interaction with sulfhydryl (-SH) group found in cellular proteins. We decided to characterize the dose-dependent effect of MeHg on the neurotoxicity and the neurite outgrowth induced effects on chick sympathetic neurons dissociated and purified in culture. In this model, MeHg inhibited neurite outgrowth (1-10 microM) and induced cell death (1-10 microM) after 48 h in culture. Since metal toxicity often generates reactive oxygen species, we tested if antioxidant compounds such as glutathione (GSH) or L-cysteine (L-cys) could block the deleterious effects promoted by MeHg. L-methionine, another sulfur-containing amino acid, but without a SH group, was also used in this work. We show that GSH (10-100 microM) and L-cys (100 microM), but not L-methionine (100 microM), fully blocked neurite degeneration and sympathetic neuron cell death in culture.
甲基汞(MeHg)与脊椎动物神经系统的多种有害影响有关,其中部分影响是通过与细胞蛋白质中的巯基(-SH)相互作用产生的。我们决定表征MeHg对神经毒性的剂量依赖性影响以及对培养中解离和纯化的鸡交感神经元神经突生长的诱导作用。在这个模型中,培养48小时后,MeHg抑制神经突生长(1 - 10微摩尔)并诱导细胞死亡(1 - 10微摩尔)。由于金属毒性常常会产生活性氧,我们测试了抗氧化化合物如谷胱甘肽(GSH)或L-半胱氨酸(L-cys)是否能阻止MeHg促进的有害影响。L-蛋氨酸,另一种含硫氨基酸,但不含巯基,也用于这项研究。我们发现GSH(10 - 100微摩尔)和L-cys(100微摩尔),而不是L-蛋氨酸(100微摩尔),能完全阻止培养中的神经突退化和交感神经元细胞死亡。