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2003 Fiscal Year Final Research Report Summary

Complex phosphate sensing system regulating phosphate homeostasis

Research Project

Project/Area Number 13470013
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionThe University of Tokushima

Principal Investigator

TAKEDA Eiji  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (00144973)

Co-Investigator(Kenkyū-buntansha) MORITA Kyouko  The University of Tokushima, School of Medicine, Research Associate, 医学部, 助手 (40244777)
YAMAMOTO Hironori  The University of Tokushima, School of Medicine, Research Associate, 医学部, 助手 (60314861)
TAKETANI Yutaka  The University of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (30263825)
OKUMURA Hisami  The University of Tokushima, School of Medicine, Research Associate, 医学部, 教務員 (30322259)
Project Period (FY) 2001 – 2003
Keywordsphosphate transporter / caveolae / translocation / parathyroid hormone / phosphate / fibroblast growth factor 23
Research Abstract

Inorganic phosphate (Pi) is required for cellular function and skeletal mineralization. Serum Pi level is maintained within a narrow range through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. Pi is abundant in the diet, and intestinal absorption of Pi is efficient and minimally regulated. In a survey in the United States and in Japan, the amount of phosphorus from food is gradually increasing. It is thought that excess amounts of phosphorus intake for long periods are a strong factor in bone impairment and ageing. The restriction of phosphorus intake seems to be important under low calcium intake to keep QOL on high level
The kidney is a major regulator of Pi homeostasis and can increase or decrease its Pi reabsorptive capacity to accommodate Pi need. The crucial regulated step in Pi homeostasis is the transport of Pi across the renal proximal tubule. Type II sodium-dependent phosphate (Na/Pi) cotr … More ansporter (NPT2) is the major molecule in the renal proximal tubule and is regulated by hormones and nonhormonal factors. Recent studies of inherited and acquired hypophosphatemia which exhibit similar biochemical and clinical features, have led to the identification of novel genes, PHEX and FGF23, that play a role in the regulation of Pi homeostasis. The PHEX gene encodes an endopeptidase, predominantly expressed in bone and teeth but not in kidney. FGF-23 may be a substrate of this endopeptidase and inhibit renal Pi reabsorption
Caveolae-like microdomains (CM) are thought to play an important role in the apical targeting and translocational regulation of NPT2 in response to parathyroid hormone (PTH). NPT2 was primarily localized in CM derived from the apical plasma membrane of OK N2 cells. PTH reduced the levels of immunoreactive NPT2 in CM ; this effect was blocked by methyl-3-cyclodextrin, an inhibitor of CM, and cytochalasin D, which depolymerizes actin. PTH activated both PKA and PKCa in CM, and increased the phosphorylation of 80 kDa and 250 kDa substrates ; we identified ezrin as a candidate protein for the 80 kDa substrate
Our results suggest that NPT2 is localized to plasma membrane CM and that these CM not only play a role in PTH-and actin-mediated regulation of NPT2 surface expression, but also in the compartmentalization of PTH-responsive signaling molecules. Thus, CM appear to be important microdomains involving phosphate sensing system regulating phosphate homeostasis Less

  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] Arai Hidekazu: "The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene."J.Bone Miner.Res.. 16. 1256-1264 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kubota Megumi: "Association between two types of vitamin D receptor gene polymorphsim and bone status in premenopausal Japanese women."Calcif.Tissue Int.. 68. 16-22 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nii Tomoko: "Direct demonstration of humorally mediated inhibition of the transcription of phosphate transporter in XLH patients."Clin.Exp.Nephrol.. 5. 144-152 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nii Tomoko: "Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation."Biochem.J.. 358. 693-704 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto Takehisa: "Hypophosphatemic rickets accompanying McCune-Albright syndrome : evidence that a humoral factor causes hypophosphatemia."J.Bone Miner.Metab.. 19. 287-295 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 森田恭子: "副甲状腺ホルモンによるリントランスポーター遺伝子の調節"CLINICAL CALCIUM. 11. 82-86 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzaki Yuki: "Hygrogen peroxide stimulates C-Src-mediated big mitogen-activated protein kinase 1 (BMK1) and the MEF2C signaling pathway in PC12 cells."J.Biol.Chem.. 277. 9614 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda Eiji: "Phosphorus supply per capita from food in Japan between 1960 and 1995."J.Nutr.Sci.Vitaminol.. 48. 102-108 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda Eiji: "Human vitamin D receptor gene expression in intestine and osteoporosis."Proceedings of the 2 nd China-Japan International Conference on vitamins. 228-239 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Pike J Wesley: "Vitamin D receptor-mediated gene regulation mechanisms and current concepts of vitamin D analog selectivity."Advances in Renal Replacement Therapy. 9. 168-174 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武田英二: "リン輸送体の分子生物学"腎と骨代謝. 15. 33-38 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 芳田美智子: "スタニオカルシン2の分泌機構"発達腎研究会誌. 10. 50-56 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taketani Yutaka: "Increase in IP3 and intracellular Ca2+ induced by phosphate depletion in LLC-PK1 cell."Biochem.Biophys.Res.Commun.. 305. 287-291 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koda Tomoko: "Higher Concentrations of Interferon-γ Enhances Uptake and Transport of Dietary Antigens by Human Intestinal Cells A Study Using Cultured Caco-2 Cells."J.Nutr.Sci.Vitaminol.. 49. 179-186 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda Naoya: "Combination treatment with 1,25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells."Mol.Cancer Ther.. 8. 739-746 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda Eiji: "The understanding in inorganic phosphate homeostasis and the role of dietary phosphorus."J.Cell.Mol.Med.. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto Hironori: "2-Methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 potently stimulates gene-specific DNA binding of the vitamin D receptor in osteoblasts."J.Biol.Chem.. 274. 31756-31765 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Pike J Wesley: "Synthetic LXXLL peptides antagonize 1,25-dihydroxyvitamin D3-dependent transcription."J.Cell.Biochem.. 88. 252-258 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda Eiji: "Renal handling of phosphate : Calcium In Internal Medicine"Springer-Verlag London Limited. 12 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武田英二: "生体におけるリンの役割と制御:腎不全とリン"日本メディカルセンター(印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arai H., Miyamoto K., Yoshida M., Yamamoto H., Taketani Y., Morita K., Kubota M., Yoshida S., Ikeda M., Watabe F., Kanemasa Y., Takeda E.: "The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene"Bone Miner.Res.. 16. 1256-1264 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kubota M., Yoshida S., Ikeda M., Okada Y., Arai H., Miyamoto K., Takeda E.: "Association between two types of vitamin D receptor gene polymorphsim and bone status in premenopausal Japanese women"Calcif.Tissue Int.. 68. 16-22 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nu T., Taketani Y., Tani Y., Ohkido I., Segawa H., Yamamoto H., Morita K., Minamitani K., Minagawa M., Yasuda T., Niimi H., Miyauchi A., Miyamoto K.Takeda E.: "Direct demonstration of humorally mediated inhibition of the transcription of phosphate transporter in XLH patients"Clin.ExNephrol.. 5. 144-152 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nii T., Segawa H., Taketani Y., Tani.Y., Ohkido M., Kishida S., Ito M., Endou H., Kanai Y., Takeda E.Miyamoto K.: "Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation"Biochem.J.. 358. 693-704 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tonai T., Shiba K., Taketani Y., Ohmoto Y., Murata K., Muraguchi M., Ohsaki H., Takeda E., Nishisho T.: "A neutrophil elastase inhibitor (ONO-5046) reduces neurologic damage after spinal cord injury in rats"J.Neurochem.. 78. 1064-1072 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto T., Miyamoto K., Ozono K., Taketani Y., Katai K., Miyauchi A., Shima M., Yoshikawa H., Yoh K., Takeda E.Okada, S.: "Hypophosphatemic rickets accompanying McCune-Albright syndrome : evidence that a humoral factor causes hypophosphatemia"J.Bone Miner.Metab. 19. 287-295 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mocha K., Iida M., Takeda E.: "Regulation of phosphate transporter gene by parathyroid hormone"CLINICAL CALCIUM. 11. 82-86 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzaki Y., Yoshizumi M., Kagami S., Koyama A.H., Taketani Y., Houchi H_, Tsuchiya K., Takeda E., Tamaki T.: "Hydorogen peroxide stimulates c-Src-mediated big mitogen-activated protein kinase 1(BMK1) and the MEF2C signaling pathway in PC12 cells"J.Biol.Chem.. 277(11). 9614-9621 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda E., Sakamoto K., Yokota K., Shinohara M., Taketani Y., Morita K., Yamamoto H., Miyamoto K., Shibayama M.: "Phosphorus supply per capita from food in Japan between 1960 and 1995"J.Nutr.Sci.Vitaminol.. 48(2). 102-108 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda E., Morita K., Taketani Y., Yamamoto H., Miyamoto K.: "Renal handling of phosphate"Calcium In Interal Medicine (Spinger-Verlag London Limited). 137-148 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Pike J.W, Yamamoto H., Shevde N.K.: "Vitamin D receptor-mediated gene regulation mechanisms and current concepts of vitamin D analog selectivity"Advances in Renal Replacement Therapy. 9(3). 168-174 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shevde N.K., Plum L.A., Clagett-Dame M., Yamamoto H., Pike J.W, DeLuka H.F.: "A potent analog of 1 α, 25dihydroxyvitamin D3 selectively induces bone formation"Proc.Natl.Acad.Sci.USA. 9(21). 13487-13491 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda E.: "Molecular biology in phosphate transporters"Kidney and Bone Metabolism. 15. 33-38 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida M., Yamamoto H., Morita K., Takeda E.: "Secretion mechanism of stannniocalcin 2"J.Devel.Nephrol.. 10. 50-56 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taketani Y, Nomoto M., Yamamoto H., Isshiki M., Morita K., Arai H., Miyamoto K., Kato S., Takeda E.: "Increase in IP3 and intracellular Ca2+ induced by phosphate depletion in LLC-PK1 cell"Biochem.Biophys.Res.Commun.. 305. 287-291 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koda T., Minami H., Ogawa T., Yamano M., Takeda E.: "Higher Concentrations of Interferon γ Enhances Uptake and Transport of Dietary Antigens by Human Intestinal Cells A Study Using Cultured Caco-2 Cells"J.Nutr.Sci.Vitaminol.. 49. 179-186 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda N., Uemura1 H., Ishiguro H., Hori M., Hosaka M., Kyo S., Miyamoto K., Takeda E.Kubota Y.: "Combination treatment with 1, 25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells"Mol.Cancer Ther.. 8. 739-746 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda E., Yamamoto H., Arai H., Taketani Y.: "The understanding in inorganic phosphate homeostasis and the role of dietary phosphorus"J.Cell Mol.Med.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto H., Shevde N.K., Warrier A., Plum L.A., DeLuca H.F, Pike J.W.: "2-Methylene-l9-nor-(20S)-1, 25-dihydroxyvitamin D3 potently stimulates gene-specific DNA binding of the vitamin D receptor in osteoblasts"J.Biol.Chem.. 278(34). 31756-31765 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Pike J.W, Pathrose P, Barmina O., Chang C-Y., McDonnell D., Yamamoto H., Shevde N.: "Synthetic LXXLL peptides antagonize 1, 25-dihydroxyvitamin D3-dependent transcription"J.Cell Biochem. 88. 252-258 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] "The role and the regulation of phosphate in the body, Renal Failure and Phosphate, Japan Medical Center"(in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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