Paraquat potentiates glutamate toxicity in immature cultures of cerebellar granule neurons.
Toxic concentrations of paraquat (0.2mM, 24h) caused death of both mature and immature cerebellar granule neurons (CGNs), which could be prevented by blockers of ionotropic glutamate receptors, or by removal of glutamine from cultural medium. Glutamate (Glu, 0.05-1mM, 24h) was highly toxic for mature CGNs while young CGNs were insensitive to the toxic effect of Glu. Measurements of the relative intracellular calcium ion concentration showed that the Glu-induced [Ca(2+)](i) rise in mature neurons was two times higher than that in young neurons. Subtoxic concentrations of paraquat did not affect the Glu-induced [Ca(2+)](i) rise in neurons, but lowered the CGNs survival only in immature cultures. These data provide evidence that oxidative stress induced by paraquat is a strong factor modulating the glutamate-induced damage to immature CGNs.
Stelmashook
Elena V
EV
Institute of Neurology, Department of Brain Research, Russian Academy of Medical Sciences, per. Obukha 5, 105064 Moscow, Russia.
Isaev
Nickolay K
NK
Zorov
Dmitry B
DB
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D006540:Herbicides / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D006540:Herbicides; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D006861:Hydrogen Peroxide; D010269:Paraquat; D002118:Calcium