In vitro toxicity induced by methylmercury on sympathetic neurons is reverted by L-cysteine or glutathione.
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.
de Melo Reis
Ricardo Augusto
RA
Laboratory Neurochemistry, Program in Neurobiology IBCCF, UFRJ, Rio de Janeiro, Brazil.
Herculano
Anderson Manoel
AM
da Silva
Maurício Castro Cabral
MC
dos Santos
Ronald Marques
RM
do Nascimento
José Luis Martins
JL
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003553:Cystine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology*; D008767:Methylmercury Compounds / Q000633:toxicity*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000196:embryology; D013997:Time Factors
D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D003553:Cystine; D020932:Nerve Growth Factor; D005978:Glutathione