Effects of overexpression of the cytoplasmic copper-zinc superoxide dismutase on the survival of neurons in vitro.
The cytoplasmic copper-zinc superoxide dismutase (Cu, Zn SOD; SOD-1) is an abundant and well-conserved intracellular antioxidant enzyme which has been implicated in a number of oxidative stress mediated phenomena, especially Down Syndrome, in which SOD-1 activity is increased due to triplication of chromosome 21 containing the gene and, in hereditary amyotrophic lateral sclerosis, in which the gene is mutated. Overexpression of SOD-1 could theoretically, therefore, lead to increased vulnerability to oxidative stress in two distinct manners: increasing steady-state hydrogen peroxide levels or increasing toxic side reactions. We used two mouse neuronal culture systems--one in which the murine chromosome containing SOD-1 is triplicated and one in which human SOD-1 is a transgene--to test the effect of overexpression of this enzyme on antioxidant status in general and specifically on glutamate mediated oxidative stress. We found that SOD-1 overexpression increases antioxidant status at the same time it decreases vulnerability to glutamate.
Schwartz
P J
PJ
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Charlestown, USA.
Coyle
J T
JT
D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000201:enzymology*; D005978:Glutathione / Q000172:deficiency; D006801:Humans; D007608:Kainic Acid / Q000506:poisoning; D051379:Mice / Q000196:embryology; D008822:Mice, Transgenic / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D011003:Ploidies; D012016:Reference Values; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D013482:Superoxide Dismutase; D005978:Glutathione; D007608:Kainic Acid