The endogenous antioxidant glutathione as a factor in the survival of physically injured mammalian spinal cord neurons.
Glutathione is part of the system of cellular defenses against lipid peroxidation and other free radical-mediated damage. An established in vitro trauma model was utilized to evaluate whether glutathione is a factor in the survival of mammalian spinal cord neurons following physical injury. Cultured murine spinal neurons were subjected to a standard lesion: transection of a primary dendrite 100 microm from the perikaryon. Prior reduction of glutathione with ethacrynic acid or buthionine sulfoximine caused a dose-dependent decrease in neuronal survival 24 hours after dendrotomy. Prior glutathione augmentation with gamma-glutamylcysteine or L-2-oxo-4-thiazolidine carboxylic acid significantly increased survival, but N-acetyl-cysteine was not protective. Gamma glutamylcysteine effected the most rapid increase in glutathione (peak at 10 min), and survival was 72% +/- 10 when 0.2 mM gamma-glutamylcysteine was added immediately after dendrotomy compared with 38% +/- 4 in the control group (p < 0.0001). These results indicate that the level of glutathione is a factor in spinal cord neuron survival after physical trauma, and that glutathione augmentation may be an effective acute phase spinal cord injury (SCI) intervention strategy.
Lucas
J H
JH
Department of Physiology, College of Medicine, Ohio State University, Columbus 43210, USA.
Wheeler
D G
DG
Emery
D G
DG
Mallery
S R
SR
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005978:Glutathione / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007834:Lasers; D051379:Mice; D008854:Microscopy, Electron; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure
D000975:Antioxidants; D005978:Glutathione