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Copper/zinc superoxide dismutase overexpression promotes survival of cortical neurons exposed to neurotoxins in vitro
Author(s) -
Borg Jacques,
London Jacqueline
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10404
Subject(s) - sod1 , excitotoxicity , superoxide dismutase , nmda receptor , reactive oxygen species , chemistry , oxidative stress , dismutase , genetically modified mouse , microbiology and biotechnology , neurotoxin , biology , biochemistry , transgene , receptor , gene
Oxidative stress and excitotoxicity have been implicated as triggering factors in various neurodegenerative diseases or acute neurological insults. Cu/Zn superoxide dismutase (SOD1), a potent free radical scavenging factor, may prevent the progression of such diseases. In the present study, we show that SOD1 overexpression promoted the survival of cortical neuronal cultures originating from mice carrying the human SOD1 transgene. SOD1 overexpression significantly protected against the deleterious effect of reactive oxygen species, ceramide, or N ‐methyl‐ D ‐aspartate (NMDA). It also preserved cortical neurons against apoptosis induced by NMDA or ceramide, as revealed by a smaller increase in caspase 3 activity. SOD1 overexpression was correlated with higher SOD1 activity, and neurotoxins induced an increase in SOD1 activity in cultures from both mice. Moreover, the ratio of increase of SOD1 in cultures from nontransgenic vs. transgenic mice was similar in control cultures or following neurotoxins administration. The highest amount of neurotoxin‐induced SOD1 activity was generated by NMDA. Moreover, following exposure to hydrogen peroxide, the cytoskeletal organization was altered, as evidenced by modifications of β‐tubulin or MAP2 labelling. The fact that increased superoxide dismutase activity protected neurons suggests that appropriate control of SOD1 activity is required for neuronal survival under stressful conditions. © 2002 Wiley‐Liss, Inc.