)| PMID |
11796206 ( ) |
|---|---|
| Title | In vivo peroxidative activity of FALS-mutant human CuZnSODs expressed in yeast. |
| Abstract | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to loss of motor neurons. We previously characterized the enhanced peroxidative activity of the human familial ALS (FALS) mutants of copper-zinc superoxide dismutase (CuZnSOD) A4V and G93A in vitro. Here, a similar activity is demonstrated for human FALS CuZnSOD mutants in an in vivo model system, the yeast Saccharomyces cerevisiae. Spin trap adducts of alpha-(pyridyl-4-N-oxide)-N-tert-butylnitrone (POBN) have been measured by electron paramagnetic resonance (EPR) in yeast expressing mutant (A4V, L38V, G93A, and G93C) and wild type CuZnSOD upon addition of hydrogen peroxide to the culture. The trapped radical is a hydroxyethyl adduct of POBN, identified by spectral parameters. Mutant CuZnSODs produced greater concentrations of the trapped adduct compared to the wild type enzyme. This observation provides evidence for an oxidative radical mechanism, whereby the mutants of CuZnSOD catalyze the formation of reactive oxygen species that may be related to the development or progression of FALS. This study also presents an in vivo model system to study free radical production in FALS-associated CuZnSOD mutations. Angeles, CA 90045-8225, USA. jroe@lmu.edu |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 11 | SOD1 | SOD-1 | superoxide dismutase | sod1 | |
| 13748 | DLEU2 | deleted in lymphocytic leukemia, 2 | 1 | LEU2 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | sod1 | 1.9 | one fifth of these cases are associated with mutations in sod1 the gene that encodes human CuZnSOD 1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | severe motor neuron degenerative syndrome despite normal or above normal SOD activities 2 3 4 and 5 whereas neither transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | because in vitro remetallation may not reflect the state of SOD mutants in vivo we developed a yeast model system to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD-1 | 1.9 | Yeast strains expressing the human SOD-1 mutant genes (G93A, G93A G93C A4V and L38V or the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | were placed under the control of the wild type yeast SOD1 promoter and inserted into the high copy yeast/ yeast E |
| 13748 | DLEU2 | deleted in lymphocytic leukemia, 2 | LEU2 | 1.0 | yeast/ yeast E coli shuttle vector YEP351 which contains the LEU2 selectable marker |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | sod1 | 1.9 | plasmid was transformed into the Saccharomyces cerevisiae strain EG118 ( sod1 _amp_#x2212 which lacks the CuZnSOD polypeptide |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | sod1 | 1.9 | human and FALS mutant CuZnSOD proteins were expressed in an sod1 _amp_#x2212 strain of the yeast Saccharomyces cerevisiae in order to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | of expression of the CuZnSOD proteins as well as the SOD activities of crude cytosol preparations were similar in the strains |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | those expressing FALS mutant CuZnSODs although slightly higher levels of SOD activity were sometimes found for the strains expressing the human |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | in the copper site of the enzyme and is fully SOD active 11 making it highly likely that the same situation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | we previously characterized the enhanced peroxidative activity of the human familial als fals mutants of copper zinc superoxide dismutase cuznsod a4v and g93a in vitro. |