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A novel polymorphism-driven transcriptional regulation of human glyoxalase 1 gene

Research Project

Project/Area Number 16K19031
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionKanazawa University

Principal Investigator

Harashima Ai  金沢大学, 医学系, 助教 (50705522)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords転写調節
Outline of Final Research Achievements

Detoxifying enzyme glyoxalase 1 (GLO1) is known to be involved in the development of diabetes and its complications. However, the transcriptional regulation of GLO1 is not yet fully understood. In this study, we have identified novel polymorphisms in the human GLO1 promoter region. One of the polymorphisms was found to significantly upregulate the transcription of GLO1. We next addressed to reveal molecular mechanisms under the upregulation of the GLO1 transcription. As a result, the recruitment of histone proteins and the epigenetic modifications were involved in the transcriptional regulation. Cell culture conditions such as high glucose concentration or normoxia could change the frequency of the polymorphisms of the GLO1 gene. The polymorphisms were also found to link to the development of advanced diabetic vascular complications. These findings will offer a possible new avenue for the prevention and the treatment of GLO1-related diseases.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2018 2017 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] In vitro anticancer effects of a RAGE inhibitor discovered using a structure-based drug design system.2018

    • Author(s)
      El-Far A, Munesue S, Harashima A, Sato A, Shindo M, Nakajima S, Inada M, Tanaka M, Takeuchi A, Tsuchiya H, Yamamoto H, Shaheen HME, El-Sayed YS, Kawano S, Tanuma S, Yamamoto Y
    • Journal Title

      Oncology Lett

      Volume: 15 Pages: 4627-4634

    • NAID

      120006605140

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-tumor effects of a non-steroidal anti-inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator-activated receptor gamma and suppressing matrix metalloproteinase-2 expression.2018

    • Author(s)
      Higuchi T, Takeuchi, A, Munesue S, Yamamoto N, Hayashi K, Kimura H, Miwa S, Inatani H, Shimozaki S, Kato T, Aoki Y, Abe K, Taniguchi Y, Aiba H, Murakami H, Harashima A, Yamamoto Y, Tsuchiya H
    • Journal Title

      Cancer Med

      Volume: in press

    • NAID

      120006605139

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Journal Article] Perception of pathogenic bacteria by pattern recognition receptor RAGE in the frontline.2017

    • Author(s)
      Harashima A, Yamamoto Y
    • Journal Title

      IMARS Highlights

      Volume: 12 Pages: 5-7

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Intestinal transepithelial permeability of oxytocin into the blood is dependent on the receptor for advanced glycation end products in mice.2017

    • Author(s)
      Higashida H, Furuhara K, Yamauchi AM, Deguchi K, Harashima A, Munesue S, Lopatina O, Gerasimenko M, Salmina AB, Zhang JS, Kodama H, Kuroda H, Tsuji C, Suto S, Yamamoto H, Yamamoto Y
    • Journal Title

      Sci Rep

      Volume: 11 Pages: 1-15

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer.2017

    • Author(s)
      Yamaguchi T, Fushida S, Yamamoto Y, Tsukada T, Kinoshita J, Oyama K, Miyashita T, Tajima H, Ninomiya I, Munesue S, Harashima A, Harada S, Yamamoto H and Ohta T.
    • Journal Title

      Oncology Rep

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Contribution of methylglyoxal to delayed healing of bone injury in diabetes.2017

    • Author(s)
      Aikawa T, Matsubara H, Ugaji S, Shirakawa J, Nagai R, Munesue S, Harashima A, Yamamoto Y and Tsuchiya H.
    • Journal Title

      Mol Med Rep

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preventive effect of salicylate and pyridoxamine on diabetic nephropathy2016

    • Author(s)
      Abouzed TK, Munesue S, Harashima A, Masuo Y, Kato Y, Kahilo KK, Yamamoto H, Yamamoto Y
    • Journal Title

      J. Diabetes Res

      Volume: 1786789 Pages: 1-10

    • DOI

      10.1155/2016/1786789

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination.2015

    • Author(s)
      Yamaguchi T, Fushida S, Yamamoto Y, Tsukada T, Kinoshita J, Oyama K, Miyashita T, Tajima H, Ninomiya I, Munesue S, Harashima A, Harada S, Yamamoto H, Ohta T.
    • Journal Title

      Gastric Cancer

      Volume: 18 Issue: 4 Pages: 1-14

    • DOI

      10.1007/s10120-015-0579-8

    • NAID

      40020959187

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Novel polymorphisms in promoter region of human glyoxalase 1 regulate its transcription and are associated with aging-related diseases2017

    • Author(s)
      Ai Harashima, Seiichi Munesue, Junnosuke Miura, Yasuko Uchigata, Hiroshi Yamamoto, Yasuhiko Yamamoto
    • Organizer
      Keystone Symposia Conference Aging and Mechanisms of Aging-Related Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗炎症薬サリチル酸と抗糖化薬ピリドキサミンによるマウス糖尿病腎症予防効果の比較検討2017

    • Author(s)
      棟居聖一、Tarek Kamal Abouzed、原島愛、山本博、山本靖彦
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 線維肉腫細胞の悪性化形質に及ぼす新規RAGE阻害薬の効果の検討2017

    • Author(s)
      棟居聖一、原島 愛、武内章彦、田中麻莉子、河野修平、佐藤 聡、新藤実香、中島槙吾、稲田 愛、田沼 靖一、山本靖彦
    • Organizer
      第27回メイラード学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] RAGE切断を誘導する薬剤スクリーニングと疾患の制御2017

    • Author(s)
      河野 修平、宮澤 英恵、棟居 聖一、原島 愛、Duong Thi Minh Thoa、 Nontaphat Leerach、山本 靖彦
    • Organizer
      第27回メイラード学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規RAGE阻害薬による線維肉腫細胞腫瘍悪性の抑制効果の検討2017

    • Author(s)
      棟居聖一、ALI HAFEZ ALI MOHAMMED EL-FAR、原島 愛、武内章彦、河野修平、田中麻莉子、佐藤 聡、中島槙吾、田沼靖一、山本靖彦
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗炎症薬サリチル酸と抗糖化薬ピリドキサミンによるマウス糖尿病腎症予防効果の検討2017

    • Author(s)
      原島 愛、棟居聖一、Tarek Kamal Abouzed、河野修平、田中麻莉子、増尾友佑、加藤将夫、山本 博、山本靖彦
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトGlyoxalase1 (GLO1)の新規ホモポリマー遺伝子多型による転写調節機構2016

    • Author(s)
      原島 愛、棟居聖一、山本靖彦
    • Organizer
      第26回日本メイラード学会年会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
  • [Presentation] RAGE阻害薬の腫瘍悪性形成に及ぼす効果の検討2016

    • Author(s)
      棟居聖一、原島 愛、武内章彦、佐藤 聡、中島槙吾、田沼靖一、山本靖彦
    • Organizer
      第26回日本メイラード学会年会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
  • [Presentation] Glyoxalase1 promoter polymorphism regulates gene transcription 抗糖化酵素Glyoxalase 1のプロモーター遺伝子多型による転写調節機構2016

    • Author(s)
      原島 愛、棟居聖一、山本博、山本靖彦
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター・東北大学川内北キャンパス
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 乳児の社会脳発達促進用栄養組成物2017

    • Inventor(s)
      山本靖彦、原島 愛、他2名
    • Industrial Property Rights Holder
      山本靖彦、原島 愛、他2名
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-03-14
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] GLO1の発現が関与する疾患の存在の検出方法、該検出方法にに使用するマーカー、GLO1酵素活性向上剤およびGLO1酵素活性低減剤2016

    • Inventor(s)
      山本靖彦、原島 愛、他8名
    • Industrial Property Rights Holder
      山本靖彦、原島 愛、他8名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-096027
    • Filing Date
      2016-05-12
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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