Stability of mutant superoxide dismutase-1 associated with familial amyotrophic lateral sclerosis determines the manner of copper release and induction of thioredoxin in erythrocytes.
We analyzed mutant superoxide dismutase-1 (SOD-1) in erythrocytes from patients with familial amyotrophic lateral sclerosis (FALS) by using ion exchange chromatography and HPLC/electrospray ionization mass spectrometry and were able to divide mutant SOD-1 proteins into a stable form including G37R and H46R, and an unstable form including I149T and a two base pair deletion mutant. Each mutant sample showed abnormal copper peaks in different chromatographic fractions without relation to SOD-1 activities. In addition, thioredoxin, known as an antioxidant molecule, was markedly increased in the stable form but not in the unstable form. These results suggest the presence of different pathways leading to motor neuron death between stable and unstable mutants.
Ogawa
Y
Y
Department of Neurology, Osaka University Medical School, Japan.
Kosaka
H
H
Nakanishi
T
T
Shimizu
A
A
Ohoi
N
N
Shouji
H
H
Yanagihara
T
T
Sakoda
S
S
D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology / Q000235:genetics*; D003300:Copper / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology*; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D013879:Thioredoxins / Q000378:metabolism*
D013879:Thioredoxins; D003300:Copper