2010 Fiscal Year Final Research Report
The compensatory mechanism against oxidative stress in kidney dysfunction
Project/Area Number |
20590320
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pathological medical chemistry
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Research Institution | Hyogo College of Medicine |
Principal Investigator |
SUZUKI Keiichiro Hyogo College of Medicine, 医学部, 教授 (70221322)
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Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Noriko 兵庫医科大学, 医学部, 准教授 (10368532)
SAKIYAMA Haruhiko 兵庫医科大学, 医学部, 助教 (30508958)
EGUCHI Hironobu 兵庫医科大学, 医学部, 助教 (60351798)
YOSHIHARA Daisaku 兵庫医科大学, 医学部, 助教 (00567266)
YOKOE Syunichi 大阪医科大学, 医学部, 助教 (40454756)
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Co-Investigator(Renkei-kenkyūsha) |
OOKAWARA Tomomi 兵庫医療大学, 薬学部, 准教授 (50330452)
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Project Period (FY) |
2008 – 2010
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Keywords | スーパーオキシドジスムターゼ / SOD1 / SOD1ノックアウトマウス / 腎臓 / グルタチオンSトランスフェラーゼ / 酸化ストレス |
Research Abstract |
Copper/zinc-superoxide dismutase (Cu/Zn-SOD, SOD1) plays a protective role in cells by catalyzing the conversion of the superoxide anions into molecular oxygen and hydrogen peroxide. Although SOD1 knockout (KO) mice exhibit a decreased 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. The gene remarkably elevated in SOD1 KO mice kidneys was identified as the glutathione S-transferase alpha 4 gene (Gsta4), which encodes the GSTA4 subunit. The GSTA4 mRNA, protein level and activity were significantly increased in SOD1 KO mice kidneys. The administration of an iron complex, a free radical generator, induced GSTA4 mRNA and protein expression in wild-type mice kidneys. In addition, overexpression of mouse GSTA4 cDNA in human embryonic kidney cells led to a protective effect against cell death caused by both 4-hydroxynonenal and superoxide. These findings suggest that compensatory induced GSTA4 plays a protective role against oxidative stress in young SOD1 KO mice kidneys.
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[Journal Article] Induction of protective immunity by vaccination with wild-type apo SOD1 in the mutant SOD1 transgenic mice2010
Author(s)
Takeuchi S., Fujiwara N., Ido A., Ono M., Takeuchi Y., Tateno M., Suzuki K., Takahashi R., Tooyama I., Taniguchi N., Julien JP, Urushitani M.
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Journal Title
J. Neuropathol. Exp. Neurol. 69
Pages: 1044-1056
Peer Reviewed
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