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Regulation of the Na+/H+ exchanger and signal transduction

Research Project

Project/Area Number 09680642
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

WAKABAYASHI Shigeo  Dept.Mol.Physiol.NCVC, 循環分子生理部, 室長 (70158583)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Yoko  Dept.Mol.Physiol.NCVC, 循環分子生理部, 流動研究員
IKEDA Toshitaro  Dept.Mol.Physiol.NCVC, 循環分子生理部, レジデント
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsNa+ / H+ exchanger / volume regulation / calcineurin homologue protein / calmodulin / Na^+ / H^+交換輸送体 / 細胞容積 / カルシニューリン類似タンパク質 / Ca^<2+>交換輸送体 / 増殖因子 / プロテインキナーゼC / 細胞内PH / 細胞内Ca^<2+> / 情報伝達
Research Abstract

The Na/He exchanger (NHE) is an important regulator for intracellular pH (pH), C* volume, and transepithelial Na^+ transport. It exists in virtually all cells with cell ty* dependent pattern of isoform expression. Among six known isoforms of NHE, a ubiquito* isoform NHE1 is known to be rapidly activated in response to a variety of extracellul* stimuli ranging from growth factors to mechanical stimuli such as hyperosmotic stress a* cell spreading. Some accessory regulatory factors has been suggested to be involved in * regulation of NHE1. Galmodulin is the first identified regulatory factor that is involved Ca^<2+>-induced activation of NHE1. Recently, the calcineurin B homologous protein (CHP) h* been cloned as a candidate for such regulatory factors of NHE1. In recent two years, w* tried to identify CHP binding domain within NHE1. A cytoplasmic region of aa 515-530 w* identified as a strong CHP-binding domain. However, we have not yet determine t* precise role of CHP in the regulation of NHE1. We also tried to identify an important regi* of NHE for volume regulation and found that the first extracellular loop is a critical region f* positive or negative response to volume change in NHE isoforms.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Wakabayashi, S., Ikeda, T., Kobayashi, Y., Iwamoto, T., and Shigekawa, M.: "The Na+/H+ exchanger and volume regulation" In“Cell volume regulation : The moledular mechanism and volume sensing mashinery", edited. by Y. Okada, Elsevier Publishers.167-171 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwammoto, T., Pan, Y., Nakamura, T.Y., Wakabayashi, S., and: "Protein kinase C-dependent regulation of Na+/Ca2+ exchagnerisoforms NCXIa nd NCX3 does not require their direct phosphorylation." Biochemistry. 37. 17230-17238 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shigekawa, M., Ikeda, T., Iwamoto, T., and Wakabayashi, S.: "Regulatory mechanism of NHE1 isoform of Na+/H+ exchanger in crdiac and other tissues" In“Protection a gainst ischemia/reperfusion damage of the heart". Springer Verlag Tokyo. 3-21 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikeda, T., Wakabayashi, S., and Shigekawa, M.: "Mechanism of inhibition of Na+/H+ exchanger(NHE1)by ATP depletion : implications for myocardial ischmia." In“Progress in experimental cardiology", Kluwer Academic Publishers, Boston.189-197 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikeda, T., Iwamoto, T., Wakabayashi, S.. , and Shigekawa, M.: "Regulation of the Na+/H+ exchanger in fibroblasts overexpressing the Na+/Ca2+ exchanger." Am.J.Physiol.274. C1537-C1544 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwamoto, T., Wakabayashi, S., Imagawa, T. and Shigekawa, M.: "Na+/Ca2+ exchanger overexpression impairs calcium signaling in librolasts : Inhibition of the [Ca2+] increase at the cell periphery and retardation of cell adhesion." Eur.J.of Cell Biol.76. 228-236 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 若林繁夫、岩本隆宏、重川宗一: "Na+駆動性アンチポーターの構造・機能とその病態" Mebio、“チャンネルとトランスポーター", 6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakabayashi, S., Ikeda, T., Kobayashih, Y., Iwamoto, T., and Shigekawa, M.: "The Na^+/H^+ exchanger and volume regulation." In"Cell volume regulation : The molecular mechanism and volume sensing machinery", edited.by Y.Okada, Elsevier Publishers.167-171 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwamoto, T., Pan, Y., Nakamura, T.Y., Wakabayashi, S., and Shigekawa, M.: "Protein kinase C-dependent regulation of Na^+/Ca^<2+> exchanger isoforms NCX1 and NCX3 does not require their direct phosphorylation." Biochemistry. 37. 17230-17238 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shigekawa, M., Ikeda, T., Iwamoto, T., and Wakabayashi, S.: "Regulatory mechanism of NHE1 is form of Na^+/H^+ exchanger in cardiac and other tissues" In"Protection against ischemia/reperfusion damage of the heart", Springer Verlag Tokyo. 3-21 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikeda, T., Wakabayashi, S., and Shigekawa, M.: "Mechanism of inhibition o Na^+-H^+ exchanger (NHE1) by ATP depletion : implications for myocardial ischmia." in"Progress in experimental cardiology", Kluwer Academic Publishers, Boston.189-197 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikeda, T., Iwamoto, T., Wakabayashi, S., and Shigekawa, M.: "Regulation o the Na^+/H^+ exchanger in fibroblasts overexpressing the Na^+/Ca^<2+> exchanger" Am.J.Physiol.274. C1537-C1544 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwamoto, T., Wakabayashi, S., Imagawa, T., and Shigekawa, M.: "Na^+/Ca^<2+> exchanger overexpression impairs calcium signaling in fibroblasts : Inhibition of the (Ca^<2+>)increase at the cell periphery and retardation of cell adhesion." Eur.J.of Cell Biol.76. 228-236 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakabayashi, S.Ikeda, T., Iwamoto, T., Pouyssegur, J., and Shigekawa, M.: "Calmodulin-binding autoinhibitory domain controls "pH-sensing" in the Na^+/H^+ exchanger NHE1 through sequence-specific interaction." Biochemistry. 36. 12854-12861 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikeda, T., Schmitt, B., Pouyssegur, J., Wakabayashi, S., and Shigekawa, M.: "Identification of cytoplasmic subdomains that control pH-sensing of the Na^+/H exchanger (NHE1). pH-Maintenance, ATP-sensitive, and flexible loop domains" J.Biochem.(Tokyo). 121. 295-303 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakabayashi, S., Shigekawa, M., and Pouyssegur, J: "Molecular Physiology o Vertebrate Na^+/H^+ Exchangers." Physiol.Review. 77. 51-74 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakabayashi et al.: "The Na^+/H^+ exchanger and volume regulation." In “Cell volume reglation"edited by Y.Okada Elsevier Publishers. 167-171 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shigekawa,M.,Wakabayashi,S et al.: "Regulatory mechanism of NHE1 isform of Na^+/H^+ exchanger in ca〓 〓 OH〓 tissu〓" In “Protection against ischemia/reperfosion damage 16th heart",Springer Verlag Tokyo. 3-21 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikeda,T.Wakabayashi,S Shigekawa,M.: "Mechanism of inhibision Na^+/H^+ exchanger (NHE1) by Arp dipletion" In “Progress is experimental cordiology"Kluwer Academic Publishers,Boston. 189-197 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikeda,T.Wakabayashi,S.et al.: "Regulation of the Na^+/H^+ exchanger in fibroblasts overexpressing the N^+/Ca^<2+> exchangers" Am.J.Physiol.274. C1537-C1544 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iwamoto,T.et al.: "Na^+/Ca^<2+> exchanger overexpression impairs calcium signaling in fibroblasts" Eur.J.of Cell Biol.76. 228-236 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Wakabayashi et al.: "Calmuolnlin-Binding Antoinhibitory Domain Conbols "pH-sensing" in the Na^+/H^+ exchanger. NHE1 rhnugh Sejnence-Specific Enteroction." Biochemistry. 36(42). 12854-12861 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Ikeda et al.: "Regulation of the Na^+/H^+ exchanger in fibroblasts over expressing the Na^+/Ca^<2+> exchanger" Am.J.physiol.274(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Iwamoto et al.: "Na^+/Ca^<2+> over expression impairs Culcium signaling in fibroblasts : Inhibition of the [Ca^<2+>] increase it the all preriphery and retarolation of cell adhesion." European Tournal of Cell Biology. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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