Development of an assay to evaluate the reactivity at chemicals contaminated in the atmosphere, South California

• Project/Area Number: 22406004
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Environmental pharmacy
• Research Institution: University of Tsukuba
• Principal Investigator: KUMAGAI Yoshito 筑波大学, 医学医療系, 教授 (00250100)
• Co-Investigator(Kenkyū-buntansha): SHINKAI Yasuhiro 筑波大学, 医学医療系, 助教 (10454240)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 大気中揮発物質 / 親電子物質 / Keap1/Nrf2 / グルタチオン / 化学修飾 / Nrf2/Keap1システム

Research Abstract

We describe here results of studies investigating the actions of the vapor phase of ambient air samples collected in the midtown area of Los Angeles on human bronchial epithelial BEAS-2B cells using DNA microarray analysis. Among 26 genes whose expression increased 4 fold or more, 4 genes were associated with detoxifying genes regulated by the transcription factor Nrf2. Consistent with these results, the vapor samples activate the Nrf2-ARE pathway, resulting in up-regulation of heme oxygenase-1 (HO-1), glutamate cysteine ligase modifier subunit, and cystine transporter (xCT) mRNA and proteins. No appreciable increases in pro-inflammatory genes were observed. These results suggest that ambient vapor samples activate the Nrf2-ARE pathway but not an inflammatory response.

Research Products

• [Journal Article] Interaction of 9,10-phenanthraquinone with dithiol causes oxidative modification of Cu,Zn-superoxide dismutase (SOD) through redox cycling (2013)
  • Author(s): Koizumi R, Taguchi K, Hisamori M, Kumagai Y.
  • Journal Title: The Journal of Toxicological Sciences Volume: 38 Issue: 3 Pages: 317-324
  • DOI: 10.2131/jts.38.317
  • NAID: 10031158897
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed
• [Journal Article] Interaction of 9,10-phenanthraquinone with dithiol causes oxidative modification of Cu,Zn-superoxide dismutase (SOD) through redox cycling. (2013)
  • Author(s): Koizumi R
  • Journal Title: Journal of Toxicological Sciences Volume: 38
  • Peer Reviewed
• [Journal Article] A method for detecting covalent modification of sensor proteins associated with 1,4-naphthoquinone-induced activation of electrophilic signal transduction pathways (2012)
  • Author(s): Hirose R, Miura T, Sha R, Shinkai Y, Tanaka-Kagawa T, Kumagai Y.
  • Journal Title: The Journal of Toxicological Sciences Volume: 37 Issue: 5 Pages: 891-898
  • DOI: 10.2131/jts.37.891
  • NAID: 130004447003
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed
• [Journal Article] The chemical biology of naphthoquinones and its environmental implications (2012)
  • Author(s): Kumagai Y
  • Journal Title: Annual Review of Pharmacology and Toxicology Volume: 52 Issue: 1 Pages: 221-247
  • DOI: 10.1146/annurev-pharmtox-010611-134517
  • Peer Reviewed
• [Journal Article] Peroxiredoxin 6 is a molecular target for 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary epithelial A549 cells (2011)
  • Author(s): Takayama N
  • Journal Title: The Journal of Toxicological Sciences Volume: 36 Issue: 6 Pages: 817-821
  • DOI: 10.2131/jts.36.817
  • NAID: 10030037072
  • ISSN: 0388-1350, 1880-3989
  • Peer Reviewed
• [Journal Article] Initial response and cellular protection through the Keap1/Nrf2 system during exposure of primary mouse hepatocytes to 1,2-naphthoquinone (2011)
  • Author(s): Miura T, Shinkai Y, Jiang HY, Iwamoto N, Sumi D, Taguchi K, Yamamoto M, Jinno H, Tanaka-Kagawa T, Cho AK, Kumagai Y
  • Journal Title: Chem Res Toxicol Volume: 24 Issue: 4 Pages: 559-567
  • DOI: 10.1021/tx100427p
  • Peer Reviewed
• [Journal Article] Initial response and cellular protection through the Keap1/Nrf2 system during exposure of primary mouse hepatocytes to 1, 2-naphthoquinone. (2011)
  • Author(s): Miura T
  • Journal Title: Chemical Research in Toxicology Volume: 印刷中(掲載確定)
  • Peer Reviewed
• [Journal Article] Diesel exhaust particles induce a Th2 phenotype in mouse naive mononuclear cells in vitro (2010)
  • Author(s): Inoue K, Koike E, Endo A, Sumi D, Kumagai Y, Hayakawa K, Kiyono M, Tanaka M, Takano H.
  • Journal Title: Experimental and Therapeutic Medicine Volume: 1 Issue: 5 Pages: 761-767
  • DOI: 10.3892/etm.2010.129
  • Peer Reviewed
• [Journal Article] Redox and electrophilic properties ofvapor- and particle-phase components of ambient aerosols (2010)
  • Author(s): Eiguren-Fernandez A, Shinyashiki M, Schmitz DA, Distefano E, Hinds W, Kumagai Y, Cho AK, Froines JR
  • Journal Title: Environmental Research Volume: 110 Issue: 3 Pages: 207-212
  • DOI: 10.1016/j.envres.2010.01.009
  • Peer Reviewed
• [Journal Article] Biochemical and cellular effects of electrophiles present in ambient air samples (2010)
  • Author(s): Iwamoto N, Nishiyama A, Eiguren-Fernandez A, Hinds W, Kumagai Y, Froines JR, Cho AK, Shinyashiki M
  • Journal Title: Atmospheric Environment Volume: 44 Issue: 12 Pages: 1483-1489
  • DOI: 10.1016/j.atmosenv.2010.01.045
  • Peer Reviewed
• [Journal Article] Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory response to two environment pollutants: diesel exhaust particles (DEP) and 1,2-naphthoquinone (1,2-NQ) (2010)
  • Author(s): Teles AM, Kumagai Y, Brain SD, Teixeira SA, Varriano AA, Barreto MA, de Lima WT, Antunes E, Muscara MN, Costa SK.
  • Journal Title: Archives of Toxicology Volume: 84 Issue: 2 Pages: 109-117
  • DOI: 10.1007/s00204-009-0427-x
  • Peer Reviewed
• [Journal Article] Diesel exhaust particles induce a Th2 phenotype in mouse naive mononuclear cells in vitro. (2010)
  • Author(s): Inoue K
  • Journal Title: Experimental and Therapeutic Medicine Volume: 1 Pages: 761-767
  • Peer Reviewed
• [Journal Article] Redox and electrophilic properties of vapor-and particle phase components of ambient aerosols. (2010)
  • Author(s): Eiguren-Fernandez A
  • Journal Title: Environmental Research Volume: 110 Pages: 207-212
  • Peer Reviewed
• [Journal Article] Biochemical and cellular effects of electrophiles present in ambient air samples. (2010)
  • Author(s): Iwamoto N
  • Journal Title: Atmospheric Environment Volume: 44 Pages: 1483-1489
  • Peer Reviewed
• [Journal Article] Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory response to two environment pollutants diesel exhaust partitles(DEP)and 1, 2-naphthoquinone(1, 2-NQ). (2010)
  • Author(s): Teles AM
  • Journal Title: Archives of Toxicology Volume: 84 Pages: 109-117
  • Peer Reviewed
• [Presentation] Activation of Heat Shock Response during exposure of human epithelial A431 cells to an environmental electrophile, 1,4-naphthoquinone (2013)
  • Author(s): Sha R, Shinkai Y, Kumagai Y.
  • Organizer: 第12回分子予防環境医学研究会
  • Place of Presentation: つくば
  • Year and Date: 2013-02-02
• [Presentation] 環境中親電子物質によるタンパク質の化学修飾とそれに対する応答戦略 (2012)
  • Author(s): 熊谷嘉人
  • Organizer: 第39回日本毒性学会学術年会シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2012-07-19
• [Presentation] Invasion of environmental electrophiles into cells, resulting in a modulation of cellular signaltransduction pathways (2012)
  • Author(s): Kumagai Y
  • Organizer: UK-Japan Research Symposium. Molecular Mechanisms of Stress Response in Disease
  • Place of Presentation: つくば
  • Year and Date: 2012-04-07
• [Presentation] 大気中親電子物質:タンパク質の化学修飾を介した有害反応とそれに対する生体側の防御戦略 (2011)
  • Author(s): 熊谷嘉人
  • Organizer: 日本自動車研究所講演会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-25
• [Presentation] 大気中親電子物質:タンパク質の化学修飾を介した有害反応とそれに対する生体側の防御戦略 (2011)
  • Author(s): 熊谷嘉人
  • Organizer: 日本自動車研究所講演会
  • Place of Presentation: 東京都(招待講演)
  • Year and Date: 2011-11-25
• [Presentation] 環境中親電子物質に対する生体応答およびリスク軽減戦略 (2011)
  • Author(s): 熊谷嘉人.
  • Organizer: 第4回エコファーマシンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2011-02-08
• [Presentation] 環境中親電子物質に対する生体応答およびリスク軽減戦略 (2011)
  • Author(s): 熊谷嘉人
  • Organizer: 第4回エコファーマシンポジウム
  • Place of Presentation: 熊本県(熊本市)
  • Year and Date: 2011-02-08
• [Presentation] Activation of Heat Shock Response during exposure of human epithelial A431 cells to an environmental electrophile, 1,4-naphthoquinone.
  • Author(s): Liang Sha
  • Organizer: 第12回分子予防環境医学研究会
  • Place of Presentation: つくば
• [Presentation] 環境中親電子物質によるタンパク質の化学修飾とそれに対する応答戦略.
  • Author(s): 熊谷嘉人
  • Organizer: 第39回日本毒性学会学術年会シンポジウム
  • Place of Presentation: 仙台
  • Invited
• [Presentation] Invasion of environmental electrophiles into cells, resulting in a modulation of cellular signal transduction pathways. U
  • Author(s): Kumagai Y
  • Organizer: K-Japan Research Symposium. Molecular Mechanisms of Stress Response in Disease
  • Place of Presentation: つくば
  • Invited
• [Book] 改定版分子予防環境医学 (2010)
  • Author(s): 熊谷嘉人
  • Publisher: 本の泉社
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/environmental_medicine/index.html
• [Remarks] 環境生物学研究室
  • URL: http://www.md.tsukuba.ac.jp/environmental_medicine/index.html
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/environmental_medicine/index.html
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/community-med/environmentalmedicine/main/toppage.html