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1998 Fiscal Year Final Research Report Summary

Role of nitric oxide synthase in mercury toxicity

Research Project

Project/Area Number 08670385
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionUniversity of Tsukuba

Principal Investigator

KUMAGAI Yoshito  Univ.of Tsukuba Inst.of Community Med.Associate Professor, 社会医学系 (00250100)

Co-Investigator(Kenkyū-buntansha) SHIMOJO Nobuhiro  Univ.of Tsukuba Inst.of Community Med.Professor, 社会医学系, 教授 (00080622)
HOMMA Shino (TAKEDA Shino)  Univ.of Tsukuba Inst.of Community Med.Research Associate (00272203)
Project Period (FY) 1996 – 1998
Keywordsmercury / nitric oxide synthase / toxicity / alteration in gene expression
Research Abstract

Alterations in mRNA levels, protein content and enzyme activity for nitric oxide synthase (NOS) in the cerebrum and cerebellum during a continuous exposure of neurotoxic metal, methylmercury, were examined in Wistar rats. Subcutaneous (sc) administration of methylmercuric chloride (MMC, 10 mg/kg/day, 8 days) resulted in significant increases with time of NOS activities in the cerebrum (1.6-1.9-fold, 5-8 days) and cerebellum (1.4-fold, 8 days). RT-PCR and immuno-blot analyses indicated that the increase in the enzyme activity caused by this metal appears to be due to increase in protein levels of neuronal NOS (nNOS), but not inducible NOS (iNOS) because little appreciable mRNA and protein for iNOS were seen during MMC exposure. The direct effect of mercuric compounds on nNOS activity in vitro was evaluated using 20,000 g supernatant from rat cerebellum homogenate. In contrast to the in vivo observation, however, inorganic-, alkyl-, and aryl-mercuric compound showed potent inhibition of nNOS activity with IC50 values of 11-43 muM whereas dimethylmercury (DMM) was without effect on the enzyme activity. Further experiments indicated that the inhibition of nNOS by organomercurial occurred via thiol modification.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Shinyashiki M.,Kumagai Y. et al.: "Selective inhibition of the mouse brain Mn-SOD by methylmercury." Environmental Toxicolog and Pharmacology. 2. 359-366 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kumagai,Y. et al.: "Alteration in superoxide dismutase isozymes by methylmercury" Applied Organometallic Chemistry. 11. 635-643 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kumagai,Y. et al.: "Inhibition of nitric oxide formation by neuronal nitric oxide synthase by quinones : Nirtic oxidesyrthase as a quinonereductase." Chemical Research in Toxicology. 11. 608-613 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinyashiki M.,Kumagai Y.et al.: "Differential Changes in rat brain nitricoxide synthase in vivo and in vitro by methylmercury" Brain Research. 798. 147-155 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 神田洋紀 熊谷嘉人 他: "無機水銀投与によるラット腎臓中一酸化窒素合成酵素とアルギナーゼII活性の異なる変動" 産業衛生学雑誌. 40. 212-213 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kumagai Y.et al.: "Inhibition of nitricoxide formation and superoxide generation during veduetion of LY83583 by neuronal nitricoxide synthase" European Journal of Pharmacology. 360. 213-218 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kumagai Y. et al.: "The Biology of Nitric Oxide (Part6)" Moncado S,Toda N,Maeda H,Higgs EA (Eds) Portland Press (London), 1 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Midorikawa k. Kumagai Y. et al.: "The Biology of Nitric Oxide (Part6)" Moncado S,Toda N,Maeda H,Higgs EA (Eds) Portland Press (London), 1 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinyashiki, M., Kumagai, Y., Homma-Takeda, S., Nagafune, J., Suzuki, J., Matsuzaki, I., Satoh, S., Sagai, M., and Shimojo, N: "Selective inhibition of the mouse brain Mn-SOD by methylmercury" Environmental Toxicology and Pharmacology. 2. 359-366 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kumagai, Y., Homma-Takeda, S., Shinyashiki, M., and Shimojo, N: "Alteration in superoxide dismutase isozymes by methylmercury" Applied Organometallic Chemistry. 11. 635-643 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kumagai, Y., Nakajima, H., Midorikawa, K., Homma-Takeda, S., and Shimojo, N.: "Inhibition of nitric oxide formation by neuronal nitric oxide synthase by quinones : Nitric oxide synthase as a quinone reductase" Chemical Research in Toxicology. 11. 608-613 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinyashiki, M., Kumagai, Y., Nakajima, H,Nagafune, J., Homma-Takeda, S., Sagai, M., and Shimojo, N: "Differential changes in rat brain nitric oxide synthase in vivo and in vitro by methylmercury" Brain Research. 798. 147-155 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kumagai, Y., Midorikawa, K., Nakai, Y., Yoshikawa, T., Kushida, K., Homma-Takeda, S., and Shimojo, N: "Inhibition of nitric oxide formation and superoxide generation during reduction of LY83583 by neuronal nitric oxide synthase" European Journal of Pharmacology. 360. 213-218 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] "Differential alteration in nitric oxide synthase and arginase II in rat kidney by inorganic mercury" Journal Occupational Health (Japanese). 40. 212-213 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kumagai, Y., Nakajima, H., Hayashi, T., Iguchi, A., Homma-Takeda, S., and Shimojo, N: The inhibition mechanism of NO formation by nNOS by phenanthraquinone, The Biology of Nitric Oxide Part 6, Moncada, S., Toda, N., Maeda, H., Higgs, E.A.(Edt.), 67. Portland Press, London, (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Midorikawa, K., Kumagai, Y., Yoshikawa, T., Homma-Takeda, S., and Shimojo, N.: Inhibition of nNOS by 6-anilino-5,8-quinolinedione (LY83583) : a mechanism involved in suppression of NO-dependent cGMP content.The Biology of Nitric Oxide Part6, Moncada, S., Toda, N., Madea, H.Higgs, E.A.(Edt.), 65. Portland Press, London, (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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