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The compensatory mechanism against oxidative stress in kidney dysfunction

Research Project

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
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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 / Cu/Zn-SODノックアウトマウス / ヒドロキシノネナール / 過酸化脂質 / 鉄 / スーパーオキドジスムターゼ / Cu / Zn-SODノックアウトマウス
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.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (40 results)

All 2011 2010 2009 2008

All Journal Article (16 results) (of which Peer Reviewed: 8 results) Presentation (22 results) Book (2 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

    • Related Report
      2010 Final Research Report
    • 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

    • Related Report
      2010 Final Research Report
    • 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

    • Related Report
      2010 Final Research Report
  • [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

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antioxidants : benefits and risks for long-term health2010

    • Author(s)
      Yoshihara D.
    • Journal Title

      Maturitas

      Volume: 67 Pages: 103-107

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of O-linked GlcNAc modification on the glucose response of ChREBP2010

    • Author(s)
      Sakiyama H
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 402 Pages: 784-789

    • Related Report
      2010 Annual Research Report
    • 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
    • Journal Title

      J.Neuropathol.Exp.Neurol.

      Volume: 69 Pages: 1044-1056

    • Related Report
      2010 Annual Research Report
    • 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

    • Related Report
      2010 Final Research Report
    • 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

    • Related Report
      2010 Final Research Report
  • [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

    • Related Report
      2010 Final Research Report
  • [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

    • NAID

      40019884015

    • Related Report
      2010 Final Research Report
  • [Journal Article] Protective role of glutathione S-transferase A4 induced in copper/zinc-superoxide dismutase knockout mice2009

    • Author(s)
      Yoshihara D.
    • Journal Title

      Free Radic.Biol.Med. 47

      Pages: 559-567

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ALSにおける酸化ストレスおよび酸化型SOD1の関与2009

    • Author(s)
      藤原範子
    • Journal Title

      実験医学(増刊) 27

      Pages: 140-144

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 酸化ストレスと健康2009

    • Author(s)
      江口裕伸
    • Journal Title

      生物資料分析 32

      Pages: 247-256

    • NAID

      40019884015

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      江口裕伸
    • Journal Title

      運動と免疫(ナップ)

    • Related Report
      2009 Annual Research Report
  • [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

    • Related Report
      2010 Final Research Report
  • [Presentation] Changes in renal iron metabolism by SOD1 deficiency2011

    • Author(s)
      Yoshihara D.
    • Organizer
      International Symposium on Free Radical Research : Contribution to Medicine
    • Place of Presentation
      京都
    • Year and Date
      2011-01-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 2-メルカプトエタノール修飾型Cu,Zn-SODの構造解析と安定性について2010

    • Author(s)
      藤原範子
    • Organizer
      第33回日本分子生物学会第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] キメラ受容体を用いた新規抗体選択法の開発2010

    • Author(s)
      寺西佑理
    • Organizer
      第33回日本分子生物学会第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] 過酸化水素はLPSによるNO産生を増強する2010

    • Author(s)
      江口裕伸
    • Organizer
      第33回日本分子生物学会第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] 転写因子Carbohydrate Response Element-binding Protein (ChREBP)の活性化に及ぼ,すO-GlcNAc修飾及びMlxの役割2010

    • Author(s)
      崎山晴彦
    • Organizer
      第33回日本分子生物学会第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [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2010

    • Author(s)
      吉原大作
    • Organizer
      第33回日本分子生物学会第83回日本生化学会大会合同大会(BMB2010)
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] SOD1ノックアウトマウスの腎臓における鉄代謝異常2010

    • Author(s)
      吉原大作
    • Organizer
      第63回 日本酸化ストレス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2010-06-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] アセトアルデヒドはグリコアルブミン生成を抑制する2010

    • Author(s)
      崎山晴彦
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Year and Date
      2010-05-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] Oxidative modification of Cys111 residue in human Copper/zinc superoxide dismutase and its immuno-probe2009

    • Author(s)
      Fujiwara N.
    • Organizer
      The 5th Joint Meeting of The Societies For Free Radical Research Australasia and Japan
    • Place of Presentation
      Sydney University(Sydney, Australia)
    • Year and Date
      2009-12-03
    • Related Report
      2009 Annual Research Report
  • [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
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] SOD1ノックアウトマウスの腎臓における鉄の沈着とGSTA4の誘導2009

    • Author(s)
      吉原大作
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [Presentation] SOD1ノックアウトマウスにおけるGSTA4の誘導と酸化ストレス防御作用2009

    • Author(s)
      吉原大作
    • Organizer
      第62回日本酸化ストレス学会学術集会
    • Place of Presentation
      九州大学(福岡)
    • Year and Date
      2009-06-11
    • Related Report
      2009 Annual Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [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)
    • Related Report
      2010 Final Research Report
  • [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
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [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)
    • Related Report
      2010 Final Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [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
    • Publisher
      診断と治療社
    • Related Report
      2010 Final Research Report
  • [Book] 酸化ストレスの医学2008

    • Author(s)
      鈴木敬一郎
    • Total Pages
      384
    • Publisher
      診断と治療社
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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