Lead amplifies glutamate-induced oxidative stress.
Lead markedly amplified L-glutamate-induced oxidative stress, that is, increased L-glutamate-induced production of reactive oxygen species, decreased cellular glutathione, and induced cytotoxicity in human neuroblastoma cells. It was notable that oxidative burst induced by L-glutamate alone was observed only when neuronal glutathione was depleted. A role of protein kinase C (PKC) in glutamate-induced production of reactive oxygen species is likely because it was blocked by a PKC inhibitor. We suggest here that the mechanism whereby lead causes its neurotoxicity may be through the amplification of glutamate-induced oxidative stress, possibly through PKC activation.
Naarala
J T
JT
National Public Health Institute, Department of Toxicology, Kuopio, Finland.
Loikkanen
J J
JJ
Ruotsalainen
M H
MH
Savolainen
K M
KM
D002460:Cell Line; D004357:Drug Synergism; D018698:Glutamic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D007854:Lead / Q000494:pharmacology*; D009447:Neuroblastoma; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014407:Tumor Cells, Cultured
D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D007854:Lead; D018698:Glutamic Acid; D005978:Glutathione; C008261:lead acetate