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

• Project/Area Number: 16K19031
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kanazawa 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: ¥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.

Research Products

• [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
  • 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
  • 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
• [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
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Preventive effect of salicylate and pyridoxamine on diabetic nephropathy (2016)
  • 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
  • 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
  • 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 diseases (2017)
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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