E-resources
Peer reviewed
Open access
-
Andrus, Paula K.; Fleck, Timothy J.; Gurney, Mark E.; Hall, Edward D.
Journal of neurochemistry, November 1998, Volume: 71, Issue: 5Journal Article
: The Gly93→Ala mutation in the Cu,Zn superoxide dismutase (Cu,Zn‐SOD) gene (SOD1) found in some familial amyotrophic lateral sclerosis (FALS) patients has been shown to result in an aberrant increase in hydroxyl radical production by the mutant enzyme that may cause oxidative injury to spinal motor neurons. In the present study, we analyzed the extent of oxidative injury to lumbar and cervical spinal cord proteins in transgenic FALS mice that overexpress the SOD1 mutation TgN(SOD1‐G93A)G1H in comparison with nontransgenic mice. Total protein oxidation was examined by spectrophotometric measurement of tissue protein carbonyl content by the dinitrophenylhydrazine (DNPH) assay. Four ages were investigated: 30 (pre‐motor neuron pathology and clinical disease), 60 (after initiation of pathology, but pre‐disease), 100 (∼50% loss of motor neurons and function), and 120 (near complete hindlimb paralysis) days. Protein carbonyl content in 30‐day‐old TgN(SOD1‐G93A)G1H mice was twice as high as the level found in age‐matched nontransgenic mice. However, at 60 and 100 days of age, the levels were the same. Then, between 100 and 120 days of age, the levels in the TgN(SOD1‐G93A)G1H mice increased dramatically (557%) compared with either the nontransgenic mice or transgenic animals that overexpress the wild‐type human Cu,Zn‐SOD TgN(SOD1)N29. The 100–120‐day increase in spinal cord protein carbonyl levels was confirmed by sodium dodecyl sulfate‐polyacrylamide gel electrophoretic separation and western blot immunoassay, which enabled the identification of heavily oxidized individual proteins using a monoclonal antibody against DNPH‐derivatized proteins. One of the more heavily oxidized protein bands (14 kDa) was identified by immunoprecipitation as largely Cu,Zn‐SOD. Western blot comparison of the extent of Cu,Zn‐SOD protein carbonylation revealed that the level in spinal cord samples from 120‐day‐old TgN(SOD1‐G93A)G1H mice was significantly higher than that found in age‐matched nontransgenic or TgN(SOD1)N29 mice. These results suggest that the increased hydroxyl radical production associated with the G93A SOD1 mutation and/or lipid peroxidation‐derived radical species (peroxyl or alkoxyl) causes extensive protein oxidative injury and that the Cu,Zn‐SOD itself is a key target, which may compromise its antioxidant function.
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.