title: Protective role of glutathione S-transferase A4 induced in copper/zinc-superoxide dismutase knockout mice.
abstract: Copper/zinc-superoxide dismutase (SOD1) plays a protective role in cells by catalyzing the conversion of the superoxide anion into molecular oxygen and hydrogen peroxide. Although SOD1 knockout (KO) mice exhibit a reduced life span and an elevated incidence of dysfunctions in old age, young SOD1 KO mice grow normally and exhibit no abnormalities. This fact leads to the hypothesis that other antioxidative proteins prevent oxidative stress, compensating for SOD1. Differently expressed genes in 3-week-old SOD1 KO and littermate wild-type mice were explored. A gene remarkably elevated in SOD1 KO mouse kidneys was identified as the glutathione S-transferase Alpha 4 gene (Gsta4), which encodes the GSTA4 subunit. The GSTA4 protein level and activity were also significantly increased in SOD1 KO mouse kidneys. The administration of an iron complex, a free radical generator, induced GSTA4 expression in wild-type mouse kidneys. Iron deposition detected in SOD1 KO mouse kidney is thought to be an inducer of GSTA4. In addition, overexpression of mouse GSTA4 cDNA in human embryonic kidney cells decreased cell death caused by both 4-hydroxynonenal and hydrogen peroxide. These findings suggest that compensatory induced GSTA4 plays a protective role against oxidative stress in young SOD1 KO mouse kidneys.
authors.affiliation: Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yoshihara
authors.forename: Noriko
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ookawara
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kato
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sakiyama
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yokoe
authors.forename: Hironobu
authors.initials: H
authors.lastname: Eguchi
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000447:Aldehydes / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000633:toxicity; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013482:Superoxide Dismutase / Q000235:genetics*; D014018:Tissue Distribution; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000447:Aldehydes; D003432:Cross-Linking Reagents; D006861:Hydrogen Peroxide; D007501:Iron; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C027576:4-hydroxy-2-nonenal