TY - JOUR
T1 - The roles of free radicals in amyotrophic lateral sclerosis
T2 - Reactive oxygen species and elevated oxidation of protein, DNA, and membrane phospholipids
AU - Liu, Danxia
AU - Wen, Jing
AU - Liu, Jing
AU - Li, Liping
PY - 1999
Y1 - 1999
N2 - To explore whether reactive oxygen species (ROS) play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), a unique microdialysis or microcannula sampling technique was used in mice transfected with a mutant Cu,Zn-superoxide dismutase (SOD1) gene from humans with familial ALS, mice transfected with the normal human SOD1 gene, and normal mice. We demonstrate for the first time that the levels of hydrogen peroxide (H2O2) and the hydroxyl radical (·OH) are significantly higher, and the level of the superoxide anion (O2·-) is significantly lower in ALS mutant mice than in controls, supporting by in vivo evidence the hypothesis that the mutant enzyme catalyzes ·OH formation by the sequence: O2·- → H2O2 → ·OH. This removes doubts regarding the relevance of elevated ROS in FALS raised by in vitro experiments. The levels of oxidation products are also significantly higher in the mutant mice than in controls, consistent with some previous reports. Only the superoxide concentration differs between two controls among all the measurements. Our findings correlate in vivo a gene mutation to both elevated H2O2 and ·OH and increased oxidation of cellular constituents. The elevated H2O2 in mutant mice indicates impairment of its detoxification pathways, perhaps by changed interactions between SOD1 and H2O2 detoxification enzymes. - Liu, D., Wen, J., Liu, J., Li, L. The roles of free radicals in amyotrophic lateral sclerosis: reactive oxygen species and elevated oxidation of protein, DNA, and membrane phospholipids.
AB - To explore whether reactive oxygen species (ROS) play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), a unique microdialysis or microcannula sampling technique was used in mice transfected with a mutant Cu,Zn-superoxide dismutase (SOD1) gene from humans with familial ALS, mice transfected with the normal human SOD1 gene, and normal mice. We demonstrate for the first time that the levels of hydrogen peroxide (H2O2) and the hydroxyl radical (·OH) are significantly higher, and the level of the superoxide anion (O2·-) is significantly lower in ALS mutant mice than in controls, supporting by in vivo evidence the hypothesis that the mutant enzyme catalyzes ·OH formation by the sequence: O2·- → H2O2 → ·OH. This removes doubts regarding the relevance of elevated ROS in FALS raised by in vitro experiments. The levels of oxidation products are also significantly higher in the mutant mice than in controls, consistent with some previous reports. Only the superoxide concentration differs between two controls among all the measurements. Our findings correlate in vivo a gene mutation to both elevated H2O2 and ·OH and increased oxidation of cellular constituents. The elevated H2O2 in mutant mice indicates impairment of its detoxification pathways, perhaps by changed interactions between SOD1 and H2O2 detoxification enzymes. - Liu, D., Wen, J., Liu, J., Li, L. The roles of free radicals in amyotrophic lateral sclerosis: reactive oxygen species and elevated oxidation of protein, DNA, and membrane phospholipids.
KW - Hydrogen peroxide
KW - Hydroxyl radical
KW - Mutation of Cu
KW - Superoxide anion
KW - Transgenic mouse
KW - Zn-superoxide dismutase gene
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U2 - 10.1096/fasebj.13.15.2318
DO - 10.1096/fasebj.13.15.2318
M3 - Article
C2 - 10593879
AN - SCOPUS:0032764587
SN - 0892-6638
VL - 13
SP - 2318
EP - 2328
JO - FASEB Journal
JF - FASEB Journal
IS - 15
ER -