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2010 Fiscal Year Final Research Report

The compensatory mechanism against oxidative stress in kidney dysfunction

Research Project

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Project/Area Number 20590320
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionHyogo College of Medicine

Principal Investigator

SUZUKI Keiichiro  Hyogo College of Medicine, 医学部, 教授 (70221322)

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)
Co-Investigator(Renkei-kenkyūsha) OOKAWARA Tomomi  兵庫医療大学, 薬学部, 准教授 (50330452)
Project Period (FY) 2008 – 2010
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.

  • Research Products

    (20 results)

All 2010 2009 2008

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (10 results) Book (1 results)

  • [Journal Article] The role of O-linked GlcNAc modification on the glucose response of ChREBP2010

    • Author(s)
      Sakiyama H., Fujiwara N., Noguchi T., Eguchi H., Yoshihara D., Suzuki K.
    • Journal Title

      Biochem. Biophys. Res. Commun. 402

      Pages: 784-789

    • Peer Reviewed
  • [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.
    • Journal Title

      J. Neuropathol. Exp. Neurol. 69

      Pages: 1044-1056

    • Peer Reviewed
  • [Journal Article] Benefits and risks of antioxidants for health2010

    • Author(s)
      Yoshihara D., Fujiwara N., Suzuki K.
    • Journal Title

      Maturitas 67

      Pages: 375-376

  • [Journal Article] Antioxidants : benefits and risks for long-term health2010

    • Author(s)
      Yoshihara D., Fujiwara N., Suzuki K.
    • Journal Title

      Maturitas 67

      Pages: 103-107

    • Peer Reviewed
  • [Journal Article] Protective role of glutathione S-transferase A4 induced in copper/zinc-superoxide dismutase knockout mice2009

    • Author(s)
      Yoshihara D., Fujiwara N., Ookawara T., Kato S., Sakiyama H., Yokoe S., Eguchi H., Suzuki K.
    • Journal Title

      Free Radic. Biol. Med. 47

      Pages: 559-567

    • Peer Reviewed
  • [Journal Article] Anti-oxidants for therapeutic use : why are only a few drugs in clinical use?2009

    • Author(s)
      鈴木敬一郎
    • Journal Title

      Adv. Drug Deliv. Rev. 61

      Pages: 287-289

  • [Journal Article] ALSにおける酸化ストレスおよび酸化型SOD1の関与、実験医学(増刊)2009

    • Author(s)
      藤原範子、松本紋子、鈴木敬一郎、谷口直之
    • Journal Title

      病態解明に迫る活性酸素シグナルと酸化ストレス(谷口直之監修)(羊土社) Vol.27, No.15

      Pages: 140-144

  • [Journal Article] 酸化ストレスと健康、2009

    • Author(s)
      江口裕伸、藤原範子、大河原知水、鈴木敬一郎、谷口直之
    • Journal Title

      生物資料分析 Vol.32, No.4

      Pages: 247-256

  • [Journal Article] MEDICAL TOPICS第28回、ヒトCu,Zn-SOD (SOD1)のシステイン残基の酸化的修飾とその特異抗体の開発2008

    • Author(s)
      藤原範子
    • Journal Title

      THE LUNG perspectives(メディカルレビュー社) Vol.16, No.3

      Pages: 90-95

  • [Presentation] SOD1ノックアウトマウスの腎臓における鉄代謝異常とその分子機構2009

    • Author(s)
      吉原大作、藤原範子、崎山晴彦、江口裕伸、鈴木敬一郎
    • Organizer
      第83回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      20091207-20091210
  • [Presentation] Oxidative modification of Cys111 residue in human Copper/zinc superoxide dismutase and its immuno-probe2009

    • Author(s)
      Fujiwara N., Nakano M., Kato S., Yoshihara D., Eguchi H., Sakiyama H., Taniguchi N., Suzuki K.
    • Organizer
      The 5th Joint Meeting of The Societies For Free Radical Research Australasia and Japan
    • Place of Presentation
      Sydney, Australia
    • Year and Date
      20091201-20091204
  • [Presentation] 抗酸化能を獲得した2-メルカプトエタノール修飾型Cu,Zn-SODの構造解析2009

    • Author(s)
      藤原範子、伊原健太郎、若槻壮市、谷口直之、鈴木敬一郎
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      20091021-20091024
  • [Presentation] 2ME化SOD1の結晶構造解析2009

    • Author(s)
      伊原健太郎、藤原範子、富本裕介、若槻壮市、谷口直之、鈴木敬一郎
    • Organizer
      第26回PFシンポジウム
    • Place of Presentation
      つくば
    • Year and Date
      20090324-20090325
  • [Presentation] SOD1ノックアウトマウスの腎臓における鉄代謝異常2009

    • Author(s)
      吉原大作、藤原範子、崎山晴彦、江口裕伸、鈴木敬一郎
    • Organizer
      第63回日本酸化ストレス学会学術集会
    • Place of Presentation
      神奈川
    • Year and Date
      2009-06-24
  • [Presentation] SOD1ノックアウトマウスにおけるGSTA4の誘導と生理的意義2008

    • Author(s)
      吉原大作、藤原範子、大河原知水、崎山晴彦、横江俊一、江口裕伸、鈴木敬一郎
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会(BMB2008)(p14)
    • Place of Presentation
      神戸(Late-Breaking Abstracts)
    • Year and Date
      20081209-20081212
  • [Presentation] ヒトCu/Zn-スーパーオキシドジスムターゼ(SOD1)のCys111の酸化と酸化型SOD1特異抗体の作製2008

    • Author(s)
      藤原範子、中の三弥子、大河原知水、吉原大作、横江俊一、加藤信介、谷口直之、鈴木敬一郎
    • Organizer
      第61回日本酸化ストレス学会学術集会(p66)
    • Place of Presentation
      京都(抄録)
    • Year and Date
      20080619-20080620
  • [Presentation] Cu/Zn-SODノックアウトマウスにおけるGSTA4の生理的意義2008

    • Author(s)
      吉原大作、藤原範子、大河原知水、横江俊一、崎山晴彦、鈴木敬一郎
    • Organizer
      第61回日本酸化ストレス学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      20080619-20080620
  • [Presentation] Cys111 in human copper-zinc-superoxide dismutase is a primary target for peroxidation to cysteine sulfonic acid2008

    • Author(s)
      Fujiwara N., Nakano M., Yoshihara D., Ookawara T., Eguchi H., Taniguchi N., Suzuki K.
    • Organizer
      The Gordon Research conference on Thiol-based Redox Regulation and Signaling
    • Place of Presentation
      Lucca, Italy
    • Year and Date
      20080525-20080530
  • [Presentation] GSTA4-4 as a biomarker of oxidative stress in renal tubular cells2008

    • Author(s)
      Yoshihara D., Fujiwara N., Ookawara T., Yokoe S., Suzuki K.
    • Organizer
      BOSHD2008 Biomarkers of Oxidative Stress in Health and Diseases
    • Place of Presentation
      Osaka
    • Year and Date
      20080000
  • [Book] ストレスの医学(吉川敏一監修)(CHAPTER 3, 生体の抗酸化システム(1)スーパーオキシドジスムターゼ系酸化)2008

    • Author(s)
      鈴木敬一郎、藤原範子、大河原知水
    • Total Pages
      23-30
    • Publisher
      診断と治療社

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Published: 2012-01-26   Modified: 2016-04-21  

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