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Genetic introduction of thyroid hormone transporter into the Bood-Brain-Barrier

Research Project

Project/Area Number 11557001
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field General physiology
Research InstitutionTohoku University

Principal Investigator

YAWO Hiromu  Tohoku Univ. School of Med., Neurophysiology, Professor, 大学院・医学系研究科, 教授 (00144353)

Co-Investigator(Kenkyū-buntansha) HARADA Shizuko  St. Marrianna Univ. School of Med., virology, Lecturer, 細菌学教室, 講師 (10218646)
ABE Takaaki  Tohoku Univ., School of Med., Neurophysiology, Research Associate, 大学院・医学系研究科, 助手 (80292209)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1999: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordsorganic anion transporter / Thyroid hormone transporter / adenovirus / blood-brain-barrier / choroid plexus / gene transfer / トランスポーター / 有機アニオン / プロスタグランジン / 脳・脊髄関門 / 脳・血液関門
Research Abstract

It is very important to claify the transport system via blood-brain barrier system. Recently, we have identified that organic anion transporter oatp2 and oatp3 are expressed in the choroid plexus and it transport thyroid hormones.
The aim of this study is to extablished an adenovirus-mediated gene transfer system into cells to deliver drugs in to brain. The coding region of LST-1 and LST-2, both of which have isolated by us have introduced into adenovirus vector, packaged, and transfected into HEK293 cell with adenovirus genomic DNA.The cells that produces homologous-recombinant shrieked and made plaque formation. After producing large scale infected medium, the recombinant adenovirus was purified by CsCl ultracentrifuge.
The infection titer of the purified LST-1 and LST-2 adenoviruses were measured and the IC 50 of each virus was 1.26 and 1.48 X 10^<10> pfu, respectively. When recombinant virus was applied to cultured cell line, the LST-1 and LST-2 protein was strongly expressed within 24 hr after application. The size of the band was also confirmed by Western blot analysis. The LST-1 and LST-2 expressing mammalian cell transports various organic anions as substrates and the apparent Km value of taurocholate uptake is 24 micro M and 32 micro M, respectively and both of which is a comparative value of the native cells reported. Our study revaled that our system is very effective and useful tool to deliver drugs through cell membrane.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Honda I. et al.: "Re-evaluation of phorbol ester-induced potentiation of transmitter release from mossy fibre terminals of the mouse hippocampus. "Journal of Physiology 529:763-776,2000. 529. 763-776 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Endo K. et al.: "mu-Opioid receptor inhibits N-type Ca2+ channels in the calyx presynaptic terminal of the embryonic chick ciliary ganglion."Journal of Physiology. 524. 769-781 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yawo H. et al.: "Involvement of cGMP-dependent protein kinase in adrenergic potentiation of transmitter release from the calyx-type presynaptic terminal.."Journal of fNeuroscience.. 19. 5293-5300 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yawo H: "Two components of transmitter release from the chick ciliary presynaptic terminal and their regulation by protein kinase C."Journal of Physiology. 516. 461-470 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yawo H.: "Protein kinase C potentiates transmitter release from the chick ciliary presynaptic terminal by increasing the exocytotic fusion probability."Journal of Physiology. 515. 169-180 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokui T. et al.: "Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2."Pharmaceutical Research. 16. 904-908 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe T. et al.: "Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1."J.Biol.Chem.. 274. 17159-17183 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kakyo M. et al.: "Immunohistochemical distribution and functional characterization of an organic anion transporting polypeptide2 (oatp2)."FEBS Lett.. 343-346 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kakyo M. et al.: "Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1"Gastroenterology. 117. 770-775 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honda I.Kamiya H.Yawo H.: "Re-evaluation of phorbol ester-induced potentiation of transmitter release from mossy fiber terminals of the mouse hippocampus."Journal of Physiology. 529. 763-776 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Endo K.Yawo H.: "mu-Opioid receptor inhibits N-type Ca2+ channels in the calyx presynaptic terminal of the embryonic chick ciliary ganglion."Journal of Physiology. 524 Pt 3. 769-781 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yawo H.Umemiya M.: "Functional plasticity of the presynaptic terminal."Tanpakushitsu Kakusan Koso. 45. 415-45424 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yawo H.: "Involvement of cGMP-dependent protein kinase in adrenergic potentiation of transmitter release from the calyx-type presynaptic terminal."Journal of Neuroscience. 19. 5293-5300 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yawo H.: "Two components of transmitter release from the chick ciliary presynaptic terminal and their regulation by protein kinase C."Journal of Physiology.. 516. 461-470 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yawo H.: "Protein kinase C potentiates transmitter release from the chick ciliary presynaptic terminal by increasing the exocytotic fusion probability."Journal of Physiology.. 515. 169-180 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokui T.Nakai D.Nakagomi R.Yawo H.Abe T.Sugiyama Y.: "Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2."Pharmaceutical Research. 16. 904-908 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe T.Kakyo M.Tokui T.Nakagomi R.Nishio T.Nakai D.Nomura H.Unno M.Suzuki M.Naitoh T.Matsuno S.Yawo H.: "Identification of a novel gene familyencoding human liver-specific organic anion transporter LST-1."Journal of Biological Chemistry. 274. 17159-163 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kakyo M.Sakagami H.Nishio T.Nakai D.Nakagomi R.Tokui T.Naitoh T.Matsuno S.Abe T.Yawo H.: "Immunohistochemical distribution and functional characterization of an organic anion transporting polypeptide 2 (oatp2)."FEBS Letters.. 445. 343-346 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kakyo M.Unno M.Tokui T.Nakagomi R.Nishio T.Iwasashi H.Nakai D.Seki M.Suzuki M.Naitoh T.Matsuno S.Yawo H.Abe T.: "Molecular characterzation and functional regulation of a novel rat liver-specific organic anion transporter rlst-1."Gastroenterology.. 117. 770-775 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honda I. et al.: "Re-evaluation of phorbol ester-induced potentiation of transmitter release from mossy fibre terminals of the mouse hippocampus."Journal of Physiology 529: 763-776, 2000. 529. 763-776 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Endo K. et al.: "mu-Opioid receptor inhibits N-type Ca2+ channels in the calyx presynaptic terminal of the embryonic chick ciliary ganglion."Journal of Physiology. 524. 769-781 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yawo H. et al.: "Involvement of cGMP-dependent protein kinase in adrenergic potentiation of transmitter release from the calyx-type presynaptic terminal.."Journal of Neuroscience.. 19. 5293-5300 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yawo H: "Two components of transmitter release from the chick ciliary presynaptic terminal and their regulation by protein kinase C."Journal of Physiology. 516. 461-470 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yawo H.: "Protein kinase C potentiates transmitter release from the chick ciliary presynaptic terminal by increasing the exocytotic fusion probability."Journal of Physiology. 515. 169-180 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tokui T. et al.: "Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2."Pharmaceutical Research. 16. 904-908 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe T.et al.: "Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1"J. Biol. Chem.. 274. 17159-17163 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Abe T.et al.: "Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transport thyroid hormones and taurocholate"J. Biol. Chem.. 273. 22395-22401 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kakyo M.et al.: "Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transport thyroid hormones and taurocholate"Gastroenterology. 117. 770-775 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kakyo M.et al.: "Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transport thyroid hormones and taurocholate"FEBS Lett.. 445. 343-346 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tokui T.et al.: "Pravastatin, an HMG-CoA reductase inhibitor, is transported by rat liver organic anion transporting polypeptide, oatp2"Pharmaceutical Res.. 16. 912-916 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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