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Alternative splicing of arsenic methyltransferase regulate arsenic toxicity

Research Project

Project/Area Number 24659059
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Environmental pharmacy
Research InstitutionTokushima Bunri University

Principal Investigator

SUMI Daigo  徳島文理大学, 薬学部, 准教授 (30400683)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヒ素化合物 / 選択的スプライシング / 毒性発現 / 慢性ヒ素中毒 / スプライシング / メチル化酵素 / AS3MT / As3MT / 白血病
Research Abstract

In this study, we examined whether alternative splicing of arsenic methyltransferase (AS3MT) mRNA regulates arsenic toxicity.
Exposure of arsenite to hepato-carcinoma HepG2 cells and human umbilical vein endothelial cells (HUVEC) resulted in an increase on the levels of splicing variant produced by exon-4 and -5 skipping (delta4,5).
We next examined the levels of delta4,5 AS3MT mRNA in various cells. The results indicated that the levels of delta 4,5 in keratinocyte HaCaT cells, leukemia K562 cells and T-cells Jurkat cells were lower as compared with HepG2 and esophageal Het1A cells. In addition we compared the sensitivity to arsenite exposure between HepG2, HaCaT and Het1A cells. The results showed that the sensitivity to arsenite exposure was roughly equal in HaCaT and Het1A cells in spite of the difference of the levels of delta 4,5. These results suggested that the difference of sensitivity to arsenite in the various cells was no correlation with alternative splicing of AS3MT mRNA.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (21 results)

All 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 3 results) Presentation (14 results) (of which Invited: 6 results) Remarks (2 results)

  • [Journal Article] Involvement of Nrf2 activation in the upregulation of S100A9 by exposure to inorganic arsenite2013

    • Author(s)
      Sumi, D., Shimizu, Y., and Himeno S.
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 31巻 Pages: 259-264

    • Related Report
      2013 Final Research Report
  • [Journal Article] Arsenite retards the cardiac differentiation of rat cardiac myoblast H9c2 cells.Biochem.2013

    • Author(s)
      Sumi, D., Abe, K., Himeno, S.
    • Journal Title

      Biophys. Res. Commun.

      Volume: (in press) Issue: 2 Pages: 175-179

    • DOI

      10.1016/j.bbrc.2013.05.069

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Nrf2 activation in the upregulation of S100A9 by exposure to inorganic arsenite.2013

    • Author(s)
      Sumi, D., Shimizu, Y., and Himeno S.
    • Journal Title

      Int. J. Mol. Med.

      Volume: 31 Pages: 259-264

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of Arsenic (+3 Oxidation State) Methyltransferase in Arsenic Metabolismand Toxicity2012

    • Author(s)
      Sumi, D., and Himeno S.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 35巻 Pages: 1870-1875

    • Related Report
      2013 Final Research Report
  • [Journal Article] Role of Arsenic (+3 Oxidation State) Methyltransferase in Arsenic Metabolism and Toxicity2012

    • Author(s)
      Sumi, D., and Himeno S.
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 35 Pages: 1870-1875

    • NAID

      130001872279

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 亜ヒ酸製剤の適応疾患の拡大を目指した基礎研究2014

    • Author(s)
      角大悟
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 亜ヒ酸によるナチュラルキラー細胞の機能障害2013

    • Author(s)
      角大悟, 津山博匡, 原田久美, 小川智子, 姫野誠一郎
    • Organizer
      第12回分子予防環境医学研究会
    • Place of Presentation
      つくばサイエンス・インフォメーションセンター
    • Related Report
      2013 Final Research Report
  • [Presentation] ナチュラルキラー細胞の機能に対する亜ヒ酸の影響2013

    • Author(s)
      小川智子, 津山博匡, 原田久美, 角大悟, 姫野誠一郎
    • Organizer
      日本薬学会第133年会(シンポジウム)
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] ヒ素化合物による免疫担当細胞の機能障害2013

    • Author(s)
      角大悟, 津山博匡, 原田久美, 小川智子, 姫野誠一郎
    • Organizer
      日本薬学会第133年会(シンポジウム)
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Effects of arsenic on immunological functions2013

    • Author(s)
      Daigo Sumi, Seiichiro Himeno
    • Organizer
      X. ISTERH (International Conference Trace Elements Research on Health and Diseases)
    • Place of Presentation
      京王プラザホテル
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 転写因子Evi-1の転写活性に対する亜ヒ酸の阻害作用2013

    • Author(s)
      角大悟、田村嶺、姫野誠一郎
    • Organizer
      メタルバイオサイエンス研究会2013
    • Place of Presentation
      静岡県立大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 転写因子Evi-1に対する亜ヒ酸の影響2013

    • Author(s)
      田村嶺、角大悟、姫野誠一郎
    • Organizer
      第23回金属の関与する生体関連反応シンポジウム
    • Place of Presentation
      武蔵野大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 慢性ヒ素曝露による食道への影響2013

    • Author(s)
      鶴本未有、角大悟、姫野誠一郎
    • Organizer
      第23回金属の関与する生体関連反応シンポジウム
    • Place of Presentation
      武蔵野大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 亜ヒ酸によるナチュラルキラー細胞の機能障害2013

    • Author(s)
      角大悟、津山博匡、原田久美、小川智子、姫野誠一郎
    • Organizer
      第12回分子予防環境医学研究会
    • Place of Presentation
      つくば サイエンス・インフォメーションセンター
    • Related Report
      2012 Research-status Report
  • [Presentation] ナチュラルキラー細胞の機能に対する亜ヒ酸の影響2013

    • Author(s)
      小川智子、津山博匡、原田久美、角大悟、姫野誠一郎
    • Organizer
      日本薬学会第133年会(シンポジウム)
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] ヒ素化合物による免疫担当細胞の機能障害2013

    • Author(s)
      角大悟、津山博匡、原田久美、小川智子、姫野誠一郎
    • Organizer
      日本薬学会第133年会(シンポジウム)
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Reduction of the degranulation in rat RBL- 2H3 mast cells by chronic exposure to arsenite via impairment ofstore-operated Ca2+entry2012

    • Author(s)
      Daigo Sumi, Yuri Shimizu, Seiichiro Himeno
    • Organizer
      The 6th International Congress of Asian Society of Toxicology
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Final Research Report
  • [Presentation] 亜ヒ酸のNK細胞活性化に対する免疫毒性作用2012

    • Author(s)
      角大悟, 原田久美, 小川智子, 姫野誠一郎
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Reduction of the degranulation in rat RBL-2H3 mast cells by chronic exposure to arsenite via impairment of store-operated Ca2+ entry2012

    • Author(s)
      Daigo Sumi, Yuri Shimizu, Seiichiro Himeno
    • Organizer
      The 6th International Congress of Asian Society of Toxicology
    • Place of Presentation
      仙台国際センター
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://p.bunri-u.ac.jp/lab10/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 徳島文理大学薬学部衛生化学講座

    • URL

      http://p.bunri-u.ac.jp/lab10/index.html

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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