title: Glycation proceeds faster in mutated Cu, Zn-superoxide dismutases related to familial amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of motor neurons in the spinal cord and motor cortex. It has been shown that 15-20% of patients with familial ALS (FALS) have defects in the Sod1 gene that encodes Cu, Zn-superoxide dismutase (SOD). To elucidate the pathological role of mutated Cu, Zn-SODs in FALS, the susceptibility of mutants to glycation was examined. Mutated Cu, Zn-SODs (G37R, G93A, and I113T) related to FALS and wild type were produced in a baculovirus/insect cell expression system. Glycated and nonglycated proteins were separated on a boronate column, and the nonglycated fraction was then incubated with glucose. The mutated Cu, Zn-SODs were found to be highly susceptible to glycation compared with the wild-type enzyme as estimated by Western blot analysis using an anti-hexitol lysine antibody. The mutated Cu, Zn-SOD incubated with glucose generated higher levels of hydrogen peroxide than the wild-type enzyme. Mutated Cu, Zn-SODs were also shown to be highly susceptible to fructation, and the fructated mutant also produced higher levels of hydrogen peroxide than the wild type. These results suggest that high susceptibility of mutated Cu, Zn-SODs to glycation could be the origin of the oxidative stress associated with neuronal dysfunction in FALS.
authors.affiliation: Department of Biochemistry, Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Takamiya
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Theingi
authors.initials: T
authors.lastname: Myint
authors.forename: Yong Seek
authors.initials: YS
authors.lastname: Park
authors.forename: Nobuko
authors.initials: N
authors.lastname: Miyazawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Endo
authors.forename: Noriko
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sakiyama
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Misonou
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005192:Family Health; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D005632:Fructose; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D005947:Glucose