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Regulation of vascular endothelial cell functions and exhibition of heavy metal toxicity through zinc transporter expression

Research Project

Project/Area Number 24390034
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Environmental pharmacy
Research InstitutionTokyo University of Science

Principal Investigator

Kaji Toshiyuki  東京理科大学, 薬学部, 教授 (90204388)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Chika  東邦大学, 薬学部, 教授 (70230571)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords金属輸送体 / 血管内皮細胞 / 亜鉛 / カドミウム / 細胞毒性 / 亜鉛輸送体 / サイトカイン / TGF-β / 血管平滑筋細胞 / メタロチオネイン / 生体分子 / 整理活性 / トランスポーター / 毒性学 / 金属生物学 / 生理活性
Outline of Final Research Achievements

Vascular endothelial cells are the only cell type that directly contact with blood. It was reported that organ toxicity of cadmium possibly depends on the toxicity of the metal to vascular endothelial cells; however, the mechanisms have been unclear. In the present study, we found that TGF-β, an inflammatory cytokine that can influence the cytotoxicity of cadmium to vascular endothelial cells, induces the expression of a zinc transporter ZIP8 in vascular endothelial cells. In addition, it was revealed that the expression level of ZIP8 as well as metallothionein induction is important for interaction of zinc with cadmium in the cells.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (50 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (26 results) (of which Invited: 5 results) Remarks (5 results)

  • [Journal Article] Induction of metallothionein isoforms by copper diethyldithiocarbamate in cultured vascular endothelial cells2016

    • Author(s)
      Fujie T, Segawa Y, Yoshida E, Kimura T, Fujiwara Y, Yamamoto C, Satoh M, Naka H, Kaji T.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 41 Issue: 2 Pages: 225-232

    • DOI

      10.2131/jts.41.225

    • NAID

      130005132663

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Zinc diethyldithiocarbamate as an inducer of metallothionein in cultured vascular endothelial cells2016

    • Author(s)
      Fujie T, Segawa Y, Uehara A, Nakamura T, Kimura T, Yoshida E, Yamamoto C, Uchiyama M, Naka H, Kaji T.
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 41 Issue: 2 Pages: 217-224

    • DOI

      10.2131/jts.41.217

    • NAID

      130005132664

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells.2016

    • Author(s)
      Shinkai Y, Kimura T, Itagaki A, Yamamoto C, Taguchi K, Yamamoto M, Kumagai Y, Kaji T.
    • Journal Title

      Toxicol Appl Pharmacol

      Volume: 295 Pages: 37-46

    • DOI

      10.1016/j.taap.2016.01.020

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Copper diethyldithiocarbamate as an activator of Nrf2 in cultured vascular endothelial cells.2016

    • Author(s)
      Fujie T, Murakami M, Yoshida E, Tachinami T, Shinkai Y, Fujiwara Y, Yamamoto C, Kumagai Y, Naka H, Kaji T.
    • Journal Title

      Journal of Biological Inorganic Chemistry

      Volume: 21 Issue: 2 Pages: 263-273

    • DOI

      10.1007/s00775-016-1337-z

    • NAID

      120007135582

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Heparan sulfate chains potentiate cadmium cytotoxicity in cultured vascular endothelial cells.2015

    • Author(s)
      Fujiwara Y, Yamamoto C, Yoshida A, Kumagai Y, Kaji T.
    • Journal Title

      Arch Toxicol.

      Volume: 印刷中 Issue: 2 Pages: 259-267

    • DOI

      10.1007/s00204-014-1420-6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The cytotoxicity of organobismuth compounds with certain molecular structures can be diminished by replacing the bismuth atom with an antimony atom in the molecules2015

    • Author(s)
      Kohri, K., Yoshida, E., Yasuike, S., Fujie, T., Yamamoto, C., Kaji, T.
    • Journal Title

      Journal of Toxicological Sciences

      Volume: 40 Pages: 321-327

    • NAID

      130005068415

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Comparative cytotoxicity of triphenylstibane and fluorine-substituted triarylpnictogens in cultured vascular endothelial cells2015

    • Author(s)
      Murakami, M., Fujie, T., Matsumura, M., Yoshida, E., Yamamoto, C., Fujiwara, Y., Yasuike, S., Kaji, T.
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 2 Pages: 61-66

    • NAID

      130005083360

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] カドミウムに曝露した血管内皮細胞におけるZIP8の発現2014

    • Author(s)
      髙橋涼香,山本千夏,鍜冶利幸
    • Journal Title

      薬学雑誌

      Volume: 134 Pages: 805-807

    • NAID

      130004756448

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Convenient method to assess chemical modification of protein thiols by I electronhilic metals2014

    • Author(s)
      Toyama T, Shinkai Y, Yazawa A, Kakehashi H, Kaji T and Kumagai Y.
    • Journal Title

      Chem Biol Interact

      Volume: (In press) Pages: 41-48

    • DOI

      10.1016/j.cbi.2014.02.008

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of VEGF-related proteins in cultured human brain microvascular endothelial cells and pericytes after exposure to methylmercury2013

    • Author(s)
      Hirooka, T., Yamamoto, C., Yasutake, A., Eto, K., and Kaji, T.
    • Journal Title

      JOURNAL OF TOXICOLOGICAL SCIENCES

      Volume: 38 Pages: 837-845

    • NAID

      130004447087

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A convenient method to assess chemical modification of protein thiols by electrophilic metals2013

    • Author(s)
      Toyama, T., Shinkai, Y., Kaji, T. and Kumagai, Y.
    • Journal Title

      JOURNAL OF TOXICOLOGICAL SCIENCES

      Volume: 38 Pages: 477-484

    • NAID

      10031158913

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased thrombin activity by a Congolese herbal medicine used in sicklecellanemia2013

    • Author(s)
      Nsimba, M.M., Lami, J.N., Hayakawa, Y., Yamamoto, C., and Kaji, T.
    • Journal Title

      JOURNAL OF ETHNOPHARMACOLOGY

      Volume: 148 Issue: 3 Pages: 895-900

    • DOI

      10.1016/j.jep.2013.05.038

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of a Congolese herbal medicine used in sickle cell anemia on the expression of plasminogen activators in human coronary aortic endothelial cell culture2013

    • Author(s)
      Nsimba, M.M., Yamamoto, C., Lami, J.N., Hayakawa, Y., and Kaji, T.
    • Journal Title

      JOURNAL OF ETHNOPHARMACOLOGY

      Volume: 146 Issue: 2 Pages: 594-599

    • DOI

      10.1016/j.jep.2013.01.031

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bis (L-cysteinato) zincate (II) as a coordination compound that induces metalloothionein gene transcription without inducing cell-stress-related gene transcription2012

    • Author(s)
      Kimura, T., et al.
    • Journal Title

      J.Inorg. Biochem.

      Volume: 117 Pages: 140-146

    • DOI

      10.1016/j.jinorgbio.2012.07.021

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] S-Mercuration of rat sorbitol dehydrogenase by methylmercury causes its aggregation and the release of the zinc ion from the active site2012

    • Author(s)
      Hironori Kanda, Takashi Toyama, Azusa Shinohara-Kanda, Akihiro Iwamatsu, Yasuhiro Shinkai, Toshiyuki Kaji, Makoto Kikushima, Yoshito Kumagai
    • Journal Title

      Achieves of Toxicology

      Volume: 86 Issue: 11 Pages: 1693-1702

    • DOI

      10.1007/s00204-012-0893-4

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bismuth protects against arsenite-induced inhibition of proteoglycan synthesis in cultured vascular endothelial cells2012

    • Author(s)
      Fujiwara, Y., et al.
    • Journal Title

      J. Toxicol. Sci.

      Volume: 37 Pages: 837-843

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular defense mechanisms against lead toxicity in the vascular system2012

    • Author(s)
      Shinkai, Y and Kaji, T
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 35 Pages: 1885-1891

    • NAID

      130001872282

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The cytotoxicity of methylmercury in human microvascular endothelial cells and pericytes in culture2012

    • Author(s)
      Hirooka, T. and Kaji, T.
    • Journal Title

      Biol. Pharm. Bull

      Volume: 36 Pages: 1201-1205

    • NAID

      130001872154

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro reversal of deformity and inhibition of aggregation of scikle red blood cells by two Congolese herbal medicines2012

    • Author(s)
      Nsimba, M. M., et al.
    • Journal Title

      Journal of Medical Plants Research

      Volume: 6 Pages: 4801-4808

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 重金属の血管毒性研究からバイオ元素戦略バイオオルガノメタリクスへ2015

    • Author(s)
      鍜冶利幸
    • Organizer
      第604回新潟薬科大学薬学総合セミナー
    • Place of Presentation
      新潟薬科大学(新潟県新潟市)
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 銅錯体による血管内皮細胞メタロチオネイン誘導を制御する亜鉛輸送体 ZIP72015

    • Author(s)
      森田遥香,藤江智也,中 寛史,吉田映子,鍜冶利幸
    • Organizer
      フォーラム2015:衛生薬学・環境トキシコロジー
    • Place of Presentation
      神戸学院大学(兵庫県神戸市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 亜鉛輸送体ZIP7を介した銅錯体による血管内皮細胞メタロチオネイン誘導2015

    • Author(s)
      森田遥香,藤江智也,吉田映子,鍜冶利幸
    • Organizer
      第2回東京環境健康薬学研究会
    • Place of Presentation
      東京理科大学(東京都新宿区神楽坂)
    • Year and Date
      2015-08-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 血管平滑筋細胞におけるTGF-β1による亜鉛輸送体ZIP8遺伝子の発現調節機構2015

    • Author(s)
      武正文子,吉田映子,山本千夏,藤原泰之,鍜冶利幸
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      金沢市アートホール(石川県金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] 有機-無機ハイブリッド分子を活用した血管内皮細胞のメタロチオネイン誘導機構の解明2015

    • Author(s)
      鍜冶利幸
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      ホテル日航金沢(石川県金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 有機金属化合物の細胞毒性2015

    • Author(s)
      山本千夏,安池修之,鍜冶利幸
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      金沢市アートホール(石川県金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] カドミウムの内皮細胞毒性に対する亜鉛の防御機構への金属輸送体発現の関与2014

    • Author(s)
      上原 茜,吉田 映子,山本 千夏,鍜冶 利幸
    • Organizer
      フォーラム2014 衛生薬学・環境トキシコロジー
    • Place of Presentation
      つくば国際会議場(茨城県)
    • Year and Date
      2014-09-19 – 2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 血管内皮細胞において亜鉛は金属輸送体ZIP8の発現抑制を介してカドミウムの細胞毒性を防御する2014

    • Author(s)
      上原 茜,山本 千夏,鍜冶 利幸
    • Organizer
      第41回日本毒性学会学術年会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県)
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 有機アンチモン化合物による血管内皮細胞のメタロチオネイン誘導2014

    • Author(s)
      村上正樹,藤江智也,松村実生,藤原泰之,木村朋紀,安池修之,山本千夏,佐藤雅彦,鍜冶利幸
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 血管内皮細胞に対する亜鉛とカドミウム相互作用は金属輸送体ZIP8の発現に介在される2014

    • Author(s)
      上原茜,山本千夏,鍜冶利幸
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 骨粗鬆症モデルマウスへの Zn(bpy)Cl2 の有効性評価2014

    • Author(s)
      石橋孝文,小野寺章,岡若奈,武田直也,弘内淳美,峯松真梨,矢埜みなみ,山本麻記子,米倉玲奈,安池修之,中寛史,内山真伸,佐藤雅彦,鍜冶利幸,伊藤徳夫,河合裕一
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 血管内皮細胞においてビグリカンはTGF-βと協調してSmad経路に介在されるシンデカン-4の発現を抑制する2014

    • Author(s)
      原崇人,新開泰弘,山本千夏,熊谷嘉人,鍜冶利幸
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 有機ビスマス化合物によるヒトGlyoxalase I 阻害の構造活性相関の検討2014

    • Author(s)
      高澤涼子,嶋田奈実,安池修之,鍜冶利幸,田沼靖一
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 脂肪細胞分化及び脂肪滴の蓄積を抑制する亜鉛錯体の同定2014

    • Author(s)
      峯松真梨,小野寺章,石橋孝文,岡若奈,武田直也,弘内淳美,矢埜みなみ, 山本麻記子,米倉玲奈,安池修之,中寛史,内山真伸 , 佐藤雅彦,鍜冶利幸,伊藤徳夫,河合 裕一
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] バイオオルガノメタリクスへの招待2014

    • Author(s)
      鍜冶利幸
    • Organizer
      東京理科大学総合研究機構分子連関相乗系研究部門平成25年度成果報告会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 血管内皮細胞におけるFGF-2による亜鉛トランスポーター発現の調節2013

    • Author(s)
      蜂須賀絵美,山本千夏,鍜冶利幸
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] カドミウムに曝露した血管内皮細胞におけるZIP8の発現誘導2013

    • Author(s)
      高橋涼香,藤江智也,山本千夏,鍜冶利幸
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] カドミウムの血管内皮細胞毒性2013

    • Author(s)
      山本千夏,鍜冶利幸
    • Organizer
      日本衛生学会第83回学術総会
    • Place of Presentation
      金沢(招待講演)
    • Year and Date
      2013-03-24
    • Related Report
      2012 Annual Research Report
  • [Presentation] 血管内皮細胞においてNrf2およびメタロチオネインを誘導する有機-無機ハイブリッド 分子2013

    • Author(s)
      藤江智也,中 寛史,立浪忠志,新開泰弘,山本千夏,藤原泰之,佐藤雅彦,熊谷嘉人,鍜冶利幸
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      千葉
    • Related Report
      2013 Annual Research Report
  • [Presentation] バイオオルガノメタリクス(有機-無機ハイブリッド分子のバイオロジー)とは?2013

    • Author(s)
      鍜冶利幸
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      千葉
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Cadmium selectively and strongly induces the expression of ZIP 8 1n vascular end othelial cells2012

    • Author(s)
      Takahashi S., Fujie T., Yamamoto C., Kaji T.
    • Organizer
      The 6th International Congress of Asian Society of Toxicology
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] Induction of SLC39A8 expression by FGF-2 in vascular endothelial cells2012

    • Author(s)
      Hachisuka E., Yamamoto C., Kaji T.
    • Organizer
      The 6th International Congress of Asian Society of Toxicology
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] カドミウムによる血管内皮細胞ZIP 8の誘導2012

    • Author(s)
      高橋涼香,藤江智也,山本千夏,鍛冶利幸
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-18
    • Related Report
      2012 Annual Research Report
  • [Presentation] FGF-2による血管内皮細胞の亜鉛トランスポーター発現の調節2012

    • Author(s)
      蜂須賀絵美,山本千夏,鍛冶利幸
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-18
    • Related Report
      2012 Annual Research Report
  • [Presentation] 血管内皮細胞に対するカドミウムの毒性発現機構2012

    • Author(s)
      山本千夏,鍜冶利幸
    • Organizer
      第39回日本毒性学会学術年会
    • Place of Presentation
      仙台(招待講演)
    • Year and Date
      2012-07-18
    • Related Report
      2012 Annual Research Report
  • [Presentation] Induction of metal transporter SLC39A8 by cadmium in vascular endothelial cells2012

    • Author(s)
      高橋涼香,藤江智也,山本千夏,鍛冶利幸
    • Organizer
      第22回金属の関与する生体関連反応シンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2012-05-31
    • Related Report
      2012 Annual Research Report
  • [Remarks] 東京理科大学薬学部環境健康学教室(鍜冶研究室)

    • URL

      http://www.rs.tus.ac.jp/kaji-lab/

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Remarks] 東京理科大学研究者情報データベース

    • URL

      https://www.tus.ac.jp/ridai/doc/ji/RIJIA01Detail.php?act=nam&kin=ken&diu=6347

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京理科大学環境健康学教室(鍜冶研究室)

    • URL

      http://www.rs.tus.ac.jp/kaji-lab/index_1.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.rs.tus.ac.jp/kaji-lac/index_l.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.tus.ac.jp/ridai/doc/ji/RIJIA01Detail.php?act=nam&kin=ken&diu=6347

    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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