Analysis of molecular targets of methylmercurial inhibitors

• Project/Area Number: 16K15381
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health
• Research Institution: Kitasato University
• Principal Investigator: KIYONO MASAKO 北里大学, 薬学部, 教授 (30239842)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: メチル水銀 / オレアノール酸3-グルコシド / LAT / 抗メチル水銀薬 / 環境毒性学

Outline of Final Research Achievements

Methylmercury (MeHg) is known as environmental toxicant and induces neurotoxicity. We recently found oleanolic acid 3-glucoside (OA3Glu) suppresses MeHg toxicity in vitro and in vivo. The aim of this study was to evaluate the role of large amino acid transporters (LAT1 and LAT2) in Caco-2 cells. We found that exposure to MeHg induced lat1 and lat2. In addition, OA3Glu exposure induced lat1 but not lat2. These results are suggesting that OA3Glu has the potential to induce LAT1 and reduces intracellular MeHg through the LAT1 system.

Research Products

• [Journal Article] Cytochalasin E increased the sensitivity of human lung cancer A549 cells to bortezomib via inhibition of autophagy (2018)
  • Author(s): Takanezawa Y, Nakamura R, Kojima Y, Sone Y, Uraguchi S, Kiyono M
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 498 Issue: 3 Pages: 603-608
  • DOI: 10.1016/j.bbrc.2018.03.029
  • Peer Reviewed
• [Journal Article] Sequestosome1/p62 protects mouse embryonic fibroblasts against low-dose methylercury-induced cytotoxicity and is involved in clearance of ubiquitinated proteins. (2017)
  • Author(s): Takanezawa Y, Nakamura R, Harada R, Sone Y, Uraguchi S, Kiyono M
  • Journal Title: Scientific reports Volume: 7 Issue: 1 Pages: 1-11
  • DOI: 10.1038/s41598-017-17112-8
  • Peer Reviewed / Open Access
• [Journal Article] Variation in the activity of distinct cytochalasins as autophagy inhibitiors in human lung A549 cells. (2017)
  • Author(s): Takanezawa Y, Nakamura R, Sone Y, Uraguchi S, Kobayashi K, Tomoda H, Kiyono M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 494 Issue: 3-4 Pages: 641-647
  • DOI: 10.1016/j.bbrc.2017.10.135
  • Peer Reviewed
• [Journal Article] Atg5-dependent autophagy plays a protective role against methylmercury-induced cytotoxicity. (2016)
  • Author(s): Takanezawa Y, Nakamura R, Sone Y, Uraguchi S, Kiyono M
  • Journal Title: Toxicology Letters Volume: 9 Pages: 135-141
  • DOI: 10.1016/j.toxlet.2016.09.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Autophagy and sequestosome1/p62 play a protective role against low-dose methylercury-induced cytotoxicity. (2018)
  • Author(s): Takanezawa Y, Nakamura R, Sone Y, Uraguchi S, Kiyono M
  • Organizer: The 2018 SOT Annual Meeting and ToxExpo
  • Int'l Joint Research
• [Presentation] オレアノール酸サポニン誘導体による抗メチル水銀活性の評価 (2018)
  • Author(s): 中村亮介、高根沢康一、曽根有香、浦口晋平、白畑辰弥、小林義典、清野正子
  • Organizer: 日本薬学会第１３８年会（金沢）
• [Presentation] 低濃度メチル水銀毒性防御におけるSequestosome1/p62の役割とユビキチン化タンパク質クリアランス (2018)
  • Author(s): 高根沢康一、原田遼平、中村亮介、曽根有香、浦口晋平、清野正子
  • Organizer: 日本薬学会第１３８年会（金沢）
• [Presentation] 低濃度メチル水銀はオートファジーを活性化する (2017)
  • Author(s): 高根沢康一，中村亮介，曽根有香，浦口晋平、清野正子
  • Organizer: 第26回日本臨床環境医学会学術集会
• [Presentation] メチル水銀毒性発現へのオートファジーの関与 (2017)
  • Author(s): 高根沢康一、中村亮介、曽根有香、浦口晋平、清野正子
  • Organizer: 第４４回日本毒性学会学術年会（横浜）
  • Invited
• [Presentation] メチル水銀によるMAPキナーゼの活性化とオートファジー誘導 (2017)
  • Author(s): 高根沢康一、原田遼平、中村亮介、曽根有香、浦口晋平、清野正子
  • Organizer: 生命科学系学会合同年次大会（神戸）
• [Presentation] メチル水銀によるユビキチン結合蛋白質p62の発現誘導と防御機構の解析 (2017)
  • Author(s): 原田遼平、高根沢康一、中村亮介、曽根有香、浦口晋平、清野正子
  • Organizer: 生命科学系学会合同年次大会（神戸）
• [Presentation] メチル水銀の毒性に対するAtg5依存的オートファジーによる防御機構 (2017)
  • Author(s): 高根沢康一、中村亮介、曽根有香、浦口晋平、清野正子
  • Organizer: 日本薬学会第１３７年会（仙台）
  • Place of Presentation: 仙台国際会議場（宮城県仙台市）
• [Presentation] メチル水銀の神経毒性に対するオレアノール酸3-グルコシドの効果 (2016)
  • Author(s): 中村亮介、高根沢康一、曽根有香、浦口晋平、白畑辰弥、小林義典、清野正子
  • Organizer: フォーラム2016（東京）
  • Place of Presentation: 昭和大学旗の台キャンパス（東京都品川区）
• [Presentation] Atg5依存的オートファジーによるメチル水銀毒性防御 (2016)
  • Author(s): 高根沢康一、中村亮介、曽根有香、浦口晋平、清野正子
  • Organizer: フォーラム2016（東京）
  • Place of Presentation: 昭和大学旗の台キャンパス（東京都品川区）
• [Presentation] The role of autophagy against methyl mercury toxicity. (2016)
  • Author(s): 高根沢康一、中村亮介、曽根有香、浦口晋平、清野正子
  • Organizer: NIMD フォーラム 2016
  • Place of Presentation: 水俣病記念会議場（熊本県水俣市）
  • Invited
• [Remarks] 北里大学薬学部 公衆衛生学教室
  • URL: http://www.pharm.kitasato-u.ac.jp/kouei/