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The role of Na-HCO_3 cotransporter in metastasis of renal cell carcinoma

Research Project

Project/Area Number 14571486
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionFukuoka Prefectural University (2003)
The University of Tokyo (2002)

Principal Investigator

MORIYAMA Nobuo  Fukuoka Prefectural University, Experimental Nursing, Professor, 看護学部, 教授 (80143501)

Co-Investigator(Kenkyū-buntansha) SEKI George  The University of Tokyo, Urology, Assistant Professor, 医学部附属病院, 講師 (30206619)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsrenal tubules / Na-HCO3-cotransporter / renal tubular acidosis / SLC4A4 / Xenopus oocyte / ヒト正常腎尿細管 / ヒト腎癌細胞
Research Abstract

The Na^+-HCO<3-> cotransporter (NBC-1) plays a major role in bicarbonate absorption from proximal tubules. However, which NBC-1 variant mediates proximal bicarbonate absorption has not been determined. Moreover, the localization of this cotransporter in human kidney, renal cell carcinoma (RCC) tissues, and rat kidney has not been clarified. To clarify them, immunohistochemical analysis was performed using the specific antibodies against kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters.
In Western blot analysis the expression of kNBC-1 but not of pNBC-1 was detected in normal human kidney and RCC tissues. In immunofluorescence analysis on normal renal tissues the anti-kNBC-1 antibody strongly and exclusively labeled the basolateral membranes of proximal tubules. In RCC cells, the anti-kNBC-1 antibody labeled both plasma membranes and intracellular organelles. The labeling by anti-pNBC-1 antibody was not detected in both normal kidney and RCC tissues.
Then, we determined the localization of NBC-1 variants in rat kidney. In Western blot analysis of rat kidney both anti-kNBC-1 and anti-pNBC-1 antibodies yielded a 130 kDa band. In immunohistochemical analysis the anti-kNBC-1 antibody produced a strong and exclusively basolateral labeling in proximal tubules. On the other hand, the occasional pNBC-1 labeling was detected in the apical membranes of proximal tubules. The basolateral localization of kNBC-1 as well as the localization of pNBC-1 on the basis of the brush border was further supported by electron microscopic observation.
These results are consistent with a view that kNBC-1 is the dominant variant that mediates bicarbonate reabsorption from human and rat renal proximal tubules. They also suggest that NBC-1 may have distinct roles in cancer cells.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Satoh, H., Moriyama, N., et al.: "Localization of NBC-1 isoforms in rat and human pancreas : a possible link between pNBC-1 inactivation and pancreatic dysfunction."Am.J.Physiol.Cell Physiol. 284. C729-C737 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Konno-Takahashi, N., Takeuchi, T., (4 authors), Moriyama, N., et al.: "Engineered IGF-I Expression induces glandular enlargement in the murine prostate."J.Endocrinol.. 177. 389-398 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada, H., Yamazaki, S., Moriyama N., et al.: "Localization of NBC-1 variants in human kidney and renal cell carcinoma"Biochem.Biophys.Res.Commun.. 310. 1213-1218 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nonaka, M.I., Hishikawa, Y., Moriyama, N., et al.: "Complement C4b-binding protein as a novel murine epididymal secretory protein."Biol.Reprod.. 69. 1931-1939 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inatomi J, (6 authors), Moriyama N, et al.: "Mutational and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis"Pfluegers Arch.. 448. 438-444 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Satoh, H., Moriyama, N.: "Localization of NBC-1 isoforms in rat and human pancreas: a possible link, between pNBC-1 inactivation and pancreatic dysfunction."Am. J. Physiol. Cell Physiol.. 284. C729-C737 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Konno-Takahashi, N., Takeuchi, T., (4 authors), Moriyama, N.: "Engineered IGF-I Expression induces glandular enlargement in the murine prostate."J. Endocrinol.. 177. 389-398 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada, H., Yamazaki, S., Moriyama, N.: "Localization of NBC-1 variants in human kidney and renal cell carcinoma."Biochem. Biophys. Res. Commun.. 310. 1213-1218 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nonaka, M.I., Hishikawa, Y., Moriyama, N.: "Complement C4b-binding protein as, a novel murine epididymal secretary protein."Biol. Reprod.. 69. 1931-1939 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inatomi J, (6 authors), Moriyama N: "Mutational and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis."Pfluegers Arch.. 448. 438-444 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Konno-Takahashi, N., Takeuchi, T., (4 authors), Moriyama, N., et al.: "Engineered IGF-I Expression induces glandular enlargement in the murine prostate."J.Endocrinol.. 177. 389-398 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada, H., Yamazaki, S., Moriyama, N., et al.: "Localization of NBC-1 variants in human kidney and renal cell carcinoma"Biochem.Biophys.Res.Commun.. 310. 1213-1218 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nonaka, M.I., Hishikawa, Y., Moriyama, N., et al.: "Complement C4b-binding protein as a novel murine epididymal secretory protein."Biol.Reprod.. 69. 1931-1939 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inatomi J, (6 authors), Moriyama N, et al.: "Mutational and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis"Pfluegers Arch.. Epub. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shindo, T., 10 authors.., Moriyama, N., et al.: "Renal damage and salt-dependent hypertension in aged transgenic mice overex-pressing endothelin-1"J.Molec.Med.. 80. 105-116 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shindo, T.,..16 authors.., Moriyama, N., et al.: "Kruppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling"Nature Med.. 8. 856-863 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Satoh, H., Moriyama, N., et al.: "Localization of NBC-1 isoforms in rat and human pancreas : a possible link between pNBC-1 inactivation and pancreatic dysfunction"Am.J.Physiol.Cell Physiol.. 284. C729-C737 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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