Apoptotic death in an in vitro model of neuronal oxidative stress.
1. Oxidative stress is believed to be an important mediator of neuronal cell death but the precise mechanism by which this occurs is unknown. 2. We have developed an in vitro model of neuronal oxidative stress to study the pathways by which free radicals kill neurones. 3. We have shown that oxidative stress, cystine deprivation and glutathione depletion results in cell death with the morphological and biochemical features of apoptosis. 4. Neuronal apoptosis induced by oxidative stress can be inhibited by macromolecular synthesis inhibitors. 5. This in vitro model will be a valuable tool for defining the molecular targets of toxic free radicals in neurones and, in turn, in designing rational new therapies for free radical mediated diseases.
Ratan
R R
RR
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Baraban
J M
JM
D017209:Apoptosis; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000209:etiology; D003553:Cystine / Q000378:metabolism; D005609:Free Radicals; D018698:Glutamic Acid / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000633:toxicity*
D005609:Free Radicals; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D003553:Cystine; D005978:Glutathione