Oxidative stress induces apoptosis in embryonic cortical neurons.
Glutamate-induced glutathione depletion in immature embryonic cortical neurons has been shown to lead to oxidative stress and cell death. We have used this in vitro model to investigate the mechanism(s) by which free radicals induce neuronal degeneration. We find that glutathione depletion leads to hyper-condensation and fragmentation of chromatin into spherical or irregular shapes, a morphologic signature of apoptosis. These morphologic changes are accompanied by laddering of DNA into multiple oligonucleosomal fragments and can be prevented by the antioxidants idebenone and butylated hydroxyanisole. Cell death induced by glutathione depletion can also be prevented by inhibitors of macromolecular synthesis. Taken together, these observations suggest that oxidative stress can induce apoptosis in neurons.
Ratan
R R
RR
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Murphy
T H
TH
Baraban
J M
JM
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology*; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004622:Embryo, Mammalian; D005609:Free Radicals / Q000378:metabolism; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D005978:Glutathione / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000031:analogs & derivatives
D000975:Antioxidants; D016227:Benzoquinones; D002843:Chromatin; D005609:Free Radicals; D005971:Glutamates; D009498:Neurotoxins; D014451:Ubiquinone; D003609:Dactinomycin; D002083:Butylated Hydroxyanisole; D018698:Glutamic Acid; D003513:Cycloheximide; D005978:Glutathione; C036619:idebenone