Study on a role of NMDA receptor in chemical-induced hepatotoxicity

• Project/Area Number: 23590150
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: NEMOTO Kiyomitsu 静岡県立大学, 薬学部, 准教授 (90189366)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: NMDA受容体 / 肝臓 / 肝肥大 / 環境化学物質 / 肝がん細胞 / 肝毒性 / 肝細胞障害 / 肝発がん

Outline of Final Research Achievements

The present studies demonstrated that the treatments with chemicals inducing hepatocellular hypertrophy, hepatocyte injury, and/or liver hypertrophy resulted in super-induction of NMDA receptor 2C subunit gene (Grin 2c) expression in the rat livers, suggesting that NMDA receptor plays an important role in chemical-induced hepatotoxicity. However, induced Grin2c gene expression could not be found in chemical-treated hepatic cell lines. The induction of Grin2c gene expression might result from certain cellular factors produced from different types of hepatic cells from parenchymal hepatocytes.

Research Products

• [Journal Article] Change in the gene expression of the <i>N</i>-methyl-D-aspartate receptor 2C subunit by dietary &beta;-naphthoflavone, indole-3-carbinol, or acetaminophen in the rat liver (2013)
  • Author(s): Kiyomitsu Nemoto, Ayaka Ikeda, Takahiro Tanaka, Kaoru Inoue, Midori Yoshida, Akiyoshi Nishikawa, Toshie Gamou, Wataru Habano, Shogo Ozawa, Masakuni Degawa
  • Journal Title: The Journal of Toxicological Sciences Volume: 38 Issue: 4 Pages: 611-617
  • DOI: 10.2131/jts.38.611
  • NAID: 10031178703
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed
• [Journal Article] Induced expression of hepatic <i>N</i>-methyl-D-aspartate receptor 2C subunit gene during liver enlargement induced by lead nitrate, a hepatocellular mitogen (2013)
  • Author(s): Kiyomitsu Nemoto
  • Journal Title: The Journal of Toxicological Sciences Volume: 38 Issue: 1 Pages: 127-129
  • DOI: 10.2131/jts.38.127
  • NAID: 10031138733
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed
• [Journal Article] Super-induced gene expression of the N-methyl-D-aspartate receptor 2C subunit in chemical-induced hypertrophic liver in rats (2011)
  • Author(s): Nemoto K, Tanaka T, Ikeda A, Ito S, Mizukami M, Hikida T, Gamou T, Habano W, et al
  • Journal Title: The Journal of Toxicological Sciences Volume: 36 Issue: 5 Pages: 507-514
  • DOI: 10.2131/jts.36.507
  • NAID: 10029481028
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed
• [Presentation] Super-induced gene expression of the NMDA receptor 2C subunit in chemical-induced hypertrophic liver in rats. (2011)
  • Author(s): Kiyomitsu Nemoto
  • Organizer: 70th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 名古屋
• [Presentation] 硝酸鉛で誘発されるラット肝肥大過程での NMDA 受容体 2C サブユニット遺伝子の発現亢進 (2011)
  • Author(s): 池田絢香
  • Organizer: フォーラム2011：衛生薬学・環境トキシコロジー
  • Place of Presentation: 金沢