Quinones-mediated activation of aromatic hydrocarbon receptor through its chemical modification

• Project/Area Number: 15K18906
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental and hygienic pharmacy
• Research Institution: University of Tsukuba
• Principal Investigator: ABIKO Yumi 筑波大学, 医学医療系, 助教 (80742866)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 親電子物質 / 芳香族炭化水素受容体 / チオール基 / キノン体 / 大気汚染物質 / シグナル伝達 / 環境毒性学

Outline of Final Research Achievements

Exposure of cells to electrophilic mono- and bi-cyclic quinones, but not aromatic hydrocarbons (Ahs, parent compounds of electrophiles) and quinones without covalent binding capability, to Hepa1c1c7 cells upregulated CYP1A1 through activation of aromatic hydrocarbon receptor (AhR). These findings suggest that induction of phase-I enzymes regulated by AhR by environmental electrophiles such as mono- and bi-cyclic quinones is a health risk of environmental chemicals exposure.

Research Products

• [Journal Article] Environmental electrophiles: protein adducts, modulation of redox signaling and interaction with persulfides/polysulfides. (2017)
  • Author(s): Kumagai Y, Abiko Y.
  • Journal Title: Chemical Research in Toxicology Volume: 30 Issue: 1 Pages: 203-219
  • DOI: 10.1021/acs.chemrestox.6b00326
  • Peer Reviewed / Open Access
• [Journal Article] Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator (2016)
  • Author(s): Abiko Y, Lin FY, Lee H, Puga A, Kumagai Y.
  • Journal Title: The Journal of Toxicological Sciences Volume: 41 Issue: 6 Pages: 775-781
  • DOI: 10.2131/jts.41.775
  • NAID: 130005281972
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Chemical toxicology of reactive species in the atmosphere: two decades of progress in an electron acceptor and an electrophile. (2016)
  • Author(s): Kumagai Y, Abiko Y, Luong CN.
  • Journal Title: Journal of Toxicological Sciences Volume: 41 Issue: Special Pages: SP37-SP47
  • DOI: 10.2131/jts.41.sp37
  • NAID: 130005251461
  • Peer Reviewed / Open Access
• [Journal Article] Covalent binding of quinones activates the Ah receptor in Hepa1c1c7 cells (2015)
  • Author(s): Abiko Y, Puga A, Kumagai Y.
  • Journal Title: The Journal of Toxicological Sciences Volume: 40 Issue: 6 Pages: 873-886
  • DOI: 10.2131/jts.40.873
  • NAID: 130005108871
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Biotin-PEAC5-maleimide labeling assay to detect electrophiles. (2015)
  • Author(s): Abiko Y, Luong NC, Kumagai Y.
  • Journal Title: The Journal of Toxicological Sciences Volume: 40 Issue: 3 Pages: 405-411
  • DOI: 10.2131/jts.40.405
  • NAID: 130005068421
  • Peer Reviewed / Open Access
• [Journal Article] レドックスサイクルを介して酸化ストレスを生じる大気中成分 (2015)
  • Author(s): 熊谷嘉人、安孫子ユミ
  • Journal Title: 別冊「医学のあゆみ」レドックスUPDATE Volume: - Pages: 312-317
  • Peer Reviewed
• [Presentation] 親電子性キノン化合物によるタンパク質修飾のBiotin-(PEAC)5-maleimide-ELISAを用いた検出 (2015)
  • Author(s): 安孫子ユミ、Luong Cong Nho、熊谷嘉人
  • Organizer: フォーラム2015衛生薬学・環境トキシコロジー
  • Place of Presentation: 神戸（神戸学院大学ポートアイランドキャンパス）
  • Year and Date: 2015-09-17
• [Presentation] Biotin-(PEAC)5-maleimide-ELISAを用いた親電子性キノン化合物によるタンパク質修飾の簡便アッセイの提案 (2015)
  • Author(s): 安孫子ユミ、Luong Nho Cong、熊谷嘉人
  • Organizer: 第42回日本毒性学会学術年会
  • Place of Presentation: 金沢（石川県立音楽堂、金沢市アートホール、ホテル日航金沢）
  • Year and Date: 2015-06-29