Mechanism of intracellular reactive oxygen species generation by exposure of trivalent arsenic compounds

• Project/Area Number: 19790103
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Environmental pharmacy
• Research Institution: Chiba University
• Principal Investigator: SUZUKI Noriyuki Chiba University, 大学院薬学研究院, 特任准教授 (10376379)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,620,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 環境 / 酸化ストレス / シグナル伝達

Research Abstract

近年、ヒ素の毒性が活性酸素種の生成と深く関与しているという見方が強くなってきた。この活性酸素種は、ヒ素曝露による発癌との関連から多くの研究者の注目を集めていたものの、この活性酸素種産生が細胞内の「どこで」「どのように」起こっているのか、といった詳細な分子メカニズムは不明であった。本研究において申請者は、ヒ素暴露により細胞内に生じる酸化ストレスに関して、細胞内小器官レベルで検討を行い、その分子メカニズムを明らかにすることに成功した。

Research Products

• [Journal Article] Selenium metabolism in rats with long-term ingestion of Se-methyiseie nocvsteine using enriched stable isotopes (2009)
  • Author(s): Y. Tsuji
  • Journal Title: J. Toxicol. Sci (in press)
  • Peer Reviewed
• [Journal Article] Systemic distribution and speciation of diphenylarsinic acid fed to rats (2009)
  • Author(s): H. Naranmandura
  • Journal Title: Toxicol. Appl. Pharmacol (in press)
  • Peer Reviewed
• [Journal Article] Speciation of selenomethionine metabolites in wheat germ extract. (2008)
  • Author(s): Y. Ogra, T. Kitaguchi, K. Ishiwata, N. Suzuki, T. Toida, K. T. Suzuki
  • Journal Title: Metallomics 1 Pages: 78-86
  • Peer Reviewed
• [Journal Article] Theoretical calculations and reaction analysis on the interaction of pentavalent thioarsenicals with biorelevant thiol compounds. (2008)
  • Author(s): N. Suzuki, H. Naranmandura, S. Hirano, K. T. Suzuki.
  • Journal Title: Chem. Res. Toxicol. 21 Pages: 550-553
  • Peer Reviewed
• [Journal Article] Preferential organ distribution of methylselenol source Se-methylselenocysteine relative to methylseleninic acid. (2008)
  • Author(s): K. T. Suzuki, Y. Tsuji, Y. Ohta, N. Suzuki.
  • Journal Title: Txicol. Appl. Pharmacol. 227 Pages: 76-83
  • Peer Reviewed
• [Journal Article] In vitro translation with [34S]-labeled methionine, seleno- methionine and telluro- methionine. (2008)
  • Author(s): Y. Ogra, T. Kitaguchi, N. Suzuki, K. T. Suzuki.
  • Journal Title: Anal. Bioanal. Chem. 390 Pages: 45-51
  • Peer Reviewed
• [Journal Article] Reaction mechanism underlying the in vitro transformation of thioarsenicals (2008)
  • Author(s): H. Naranmandura
  • Journal Title: Toxicol. Appl. Pharmacol 231 Pages: 328-335
  • Peer Reviewed
• [Journal Article] Speciation of selenomethionine metabolites in wheat germ extract (2008)
  • Author(s): Y. Ogra
  • Journal Title: Metallomics 1 Pages: 78-86
  • Peer Reviewed
• [Journal Article] In vitro translation with [34S]-labeled methionine, selenomethionine and tellurome thionine. (2008)
  • Author(s): Y. Ogra
  • Journal Title: Anal. Bioanal. Chem. 390 Pages: 45-51
  • Peer Reviewed
• [Journal Article] Preferential organ distribution of methylselenol source Se-methylselenocysteine relative to methylseleninic acid. (2008)
  • Author(s): K. T. Suzuki
  • Journal Title: Toxicol. Appl. Pharmacol. 227 Pages: 76-83
  • Peer Reviewed
• [Journal Article] Theoretical calculations and reaction analysis on interaction of pentavalent thioarsenicals with biorelevant thiol compounds. (2008)
  • Author(s): N. Suzuki
  • Journal Title: Chem. Res. Toxicol. 21 Pages: 550-553
  • Peer Reviewed
• [Journal Article] Identification of Selenohomo- lanthionine in Selenium- Enriched Japanese Pungent Radish. (2007)
  • Author(s): Y. Ogra, T. Kitaguchi, K. Ishiwata, N. Suzuki, Y. Iwashita, K. T. Suzuki.
  • Journal Title: J. Anal. At. Spectrom. 22 Pages: 1390-1396
  • Peer Reviewed
• [Journal Article] Identification of selenohomolanthionine in selenium-enriched Japanese pungent radish. (2007)
  • Author(s): Y. Ogra
  • Journal Title: J. Anal. At. Spectrom 22 Pages: 1390-1396
  • Peer Reviewed
• [Journal Article] Systemic distribution and speciation of diphenylarsinic acid fed to rats.
  • Author(s): H. Naranmandura, N. Suzuki, J. Takano, M. W. Tony, Y. Ogra, K. T. Suzuki and X. C. Le
  • Journal Title: Toxicol. Appl. Pharmacol. (in press)
  • Peer Reviewed
• [Journal Article] Selenium metabolism in rats with long -term ingestion of Se-methylselenocysteine using enriched stable isotopes.
  • Author(s): Y. Tsuji, N. Suzuki, K.T. Suzuki and Y. Ogra
  • Journal Title: J. Toxicol. Sci. (in press)
  • NAID: 110007160540
  • Peer Reviewed
• [Journal Article] Simultaneous tracing of multiple precursors each labeled with a different homo-elemental isotope by speciation analysis: distribution and metabolism of four parenteral selenium sources.
  • Author(s): K. T. Suzuki, C. Doi, N. Suzuki.
  • Journal Title: Pure Appl. Chem. (in press)
  • Peer Reviewed
• [Journal Article] Reaction mechanism underlying the in vitro transformation of thioarsenicals.
  • Author(s): H. Naranmandura, N. Suzuki and K. T. Suzuki.
  • Journal Title: Toxicol. Appl. Pharmacol. (In press)
  • Peer Reviewed
• [Journal Article] Simultaneous tracing of multiple precursors each labeled with a different homo-elemental isotope by speciation analysis: distribution and metabolism of four parenteral selenium sources.
  • Author(s): K. T. Suzuki
  • Journal Title: Pure Appl. Chem. (in press)
  • Peer Reviewed
• [Presentation] ヒ素の毒性発現における生体分子との相互作用 (2009)
  • Author(s): 鈴木紀行
  • Organizer: 第一回メタロミクス研究フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2009-11-28
• [Presentation] ヒ素化合物による小胞体ストレスの誘発 (2009)
  • Author(s): 鈴木紀行,小池章太,鈴木和夫
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-26
• [Presentation] ヒ素化合物の細胞内分布とその毒性発現機構に関する検討 (2009)
  • Author(s): 鈴木紀行
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-26
• [Presentation] Mechanisms Underlying Inhibition of Protein Tyrosine Phosphatase by Arsenic Exposure. (2008)
  • Author(s): N. Suzuki, A. Sakamoto, and K. T. Suzuki
  • Organizer: 4th International Conference on Metal and Genetics
  • Place of Presentation: Paris
  • Year and Date: 2008-07-21
• [Presentation] Mechanisms Underlying Inhibition of Protein Tyrosine Phospnatase by Arsenic Exnosure (2008)
  • Author(s): 鈴木紀行
  • Organizer: 4th International Conference on Metal and lienetics
  • Place of Presentation: Paris
  • Year and Date: 2008-07-21
• [Presentation] Inhibition mechanisms of protein tyrosine phosphatase by arsenic exposure. (2008)
  • Author(s): N. Suzuki, A. Sakamoto, and K. T. Suzuki
  • Organizer: 第18回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2008-06-05
• [Presentation] Inhibition mechanisms of protein tyrosine phospnatase by arsenic exposure (2008)
  • Author(s): 鈴木紀行
  • Organizer: 第18回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2008-06-05
• [Presentation] ヒ素暴露に対する生体応答におけるprotein tyrosine phosphataseの関与 (2008)
  • Author(s): 鈴木紀行、坂本亮、鈴木和夫
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-26
• [Presentation] ヒ素暴露に対する生体応答におけるprotein tyrosine phosphataseの関与 (2008)
  • Author(s): 鈴木紀行
  • Organizer: 日本薬学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-26
• [Presentation] Pentavalent thioarsenicals: Theoretical study of extraordinary interaction with biorelevant thiol compounds. (2007)
  • Author(s): 鈴木紀行
  • Organizer: International Symposium on Metallomics 2007
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-29
• [Presentation] Pentavalent thioarsenicals: Theoretical study of extraordinary interaction with biorelevant thiol compounds (2007)
  • Author(s): N. Suzuki, H. Naranmandura, and K. T. Suzuki
  • Organizer: International Symposium on Metallomics 2007
  • Place of Presentation: Nagoya
  • Year and Date: 2007-11-28
• [Presentation] Influences of trivalent arsenic compounds on mitochondrial respiratory chain and reactive oxygen species generation (2007)
  • Author(s): N. Suzuki, T. Sawada, and K. T. Suzuki
  • Organizer: 第17回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2007-06-21
• [Presentation] Influences of trivalent arsenic compounds on mitochondrial respiratory chain and reactive oxygen species generation. (2007)
  • Author(s): 鈴木紀行
  • Organizer: 第17回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2007-06-21
• [Book] ミネラルの科学と最新応用技術 (2008)
  • Author(s): 鈴木紀行、鈴木和夫
  • Publisher: シーエムシー出版
• [Book] ミネラルの科学と最新応用技術
  • Author(s): 鈴木紀行
  • Publisher: シーエムシー出版(印刷中)
• [Remarks]
  • URL: http://www.p.chiba-u.ac.jp/lab/eisei/indexj.html