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Studies on expression of bioactive substances under hypoxia and relation to diseases

Research Project

Project/Area Number 13470030
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionTohoku University

Principal Investigator

TAKAHASHI Kazuhiro  Tohoku University, Graduate School of Medicine, Associate professor, 大学院・医学系研究科, 助教授 (80241628)

Co-Investigator(Kenkyū-buntansha) TAKEDA Kazuhisa  Tohoku University, Graduate School of Medicine, Research associate, 大学院・医学系研究科, 助手 (30311559)
FUJII Yoshiaki  Tsukuba university, Tsukuba Advanced Research Alliance, Professor, 先端学際領域研究センター, 客員教授 (00098146)
SHIBAHARA Shigeki  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70206142)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥7,100,000 (Direct Cost: ¥7,100,000)
KeywordsHeme oxygenase / Hypoxia / Adrenomedullin / Transcription / Tumor / Vascular endothelial cell / Urocortin / Orexin / 血管内比 / アドレノメデジュリン / グリオブラストーマ / 内皮細胞
Research Abstract

We studied novel peptides, such as adrenomedullin, and heme Oxygenase, particularly changes of their expression under hypoxia.
1.Adrenomedullin expression was induced by hypoxia (1% O_2) in various types of cultured cells. Expression of RAMP2,a component of adrenomedullin receptor, was decreased under hypoxia in IMR-32 neuroblastoma cells, suggesting an adaptation mechanism against hypoxia.
2.Urocortin and urocortin III were expressed not only in the brain, but also in the heart. These stress hormones may act as local regulators in the heart under stresses such as ischemia and hypoxia.
3.Plasma levels of orexin-A were decreased in parallel with the severity in patients with obstructive sleep apnea hypopnea syndrome. Orexin-A in the hypothalamus may be related to the brain hypoxia due to apnea and hypopnea.
4.Plasma levels of urotensin-II, a potent vasoactive peptide, were increased in patients with chronic renal failure or diabetes mellitus. Urotensin-II is expressed in various types of tumors and stimulates cell proliferation.
5.Expression of heme oxygenase-1 had been thought to be induced by hypoxia. We found, however that expression of heme oxygenase-1 is decreased under hypoxia in certain types of human cells. Bach1 is a transcriptional factor that acts on MARE and inhibits the transcription. Bach1 was induced by hypoxia, and may act on the MARE located in the 5' upstream region (-4.5kb--4.0kb) of human heme oxygenase-1 gene. On the other hand, Heme oxygenase-1 was induced by hypoxia in other types of human cells, independently of MARE and Bach1.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] K Takahashi et al.: "Expression of urocortin III/stresscopin in human heart and kidney."Journal of Clinical Endocrinology & Metabolism. 89. 1897-1903 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K Takahashi: "Translational medicine in fish-derived peptides : From fish endocrinology to human physiology and diseases."Endocrine Journal. 51. 1-17 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K Takahashi et al.: "Suppression of cytokine-induced expression of adrenomedullin and endothelin-1 by dexamethasone in T98G human glioblastoma cells."Peptides. 24. 1053-1062 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K Takahashi et al.: "Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II."Peptides. 24. 301-306 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitamuro T et al.: "Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells."Journal of Biological Chemistry. 278. 9125-9133 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitamuro T et al.: "Differential expression of adrenomedullin and its receptor component, receptor activity modifying protein (RAMP)2 during hypoxia in cultured human neuroblastoma cells."Peptides. 22. 1795-1801 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K Takahashi et al.: "Hypothalamus and Neurohypophysis. In ; Endocrine Pathology : Differential Diagnosis and Molecular Advances. (RV Lloyd, ed.)"Humana Press. 421 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Takahashi et al.: "Expression of urocortin III/stresscopin in human heart and kidney."Journal of Clinical Endocrinology & Metabolism. 89. 1897-1903 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Takahashi: "Translational medicine in fish-derived peptides : From fish endocrinology to human physiology and diseases."Endocrine Journal. 51. 1-17 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Takahashi, et al.: "Suppression of cytokine-induced expression of adrenomedullin and endothelin-1 by dexamethasone in T98G human glioblastoma cells."Peptides. 24. 1053-1062 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Takahashi, et al.: "Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II."Peptides. 24. 301-306 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kitamuro, et al.: "Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells."Journal of Biological Chemistry. 278. 9125-9133 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Kitamuro et al.: "Differential expression of adrenomedullin and its receptor component, receptor activity modifying protein (RAMP) 2 during hypoxia in cultured human neuroblastoma cells."Peptides. 22. 1795-1801 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Takahashi, et al.: "Hypothalamus and Neurohypophysis."Endocrine Pathology : Differential Diagnosis and Molecular Advances. (RV Lloyd, ed.) (Humana Press). 421 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K Takahashi et al.: "Expression of urocortin III/stresscopin in human heart and kidney"Journal of Clinical Endocrinology & Metabolism. 89(In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] K Takahashi: "Translational medicine in fish-derived peptides : From fish endocrinology to human physiology and diseases"Endocrine Journal. 51. 1-17 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] K Takahashi: "The brainstem is a key target for neuroendocrine research on obesity"Endocrinology. 144. 4690-4691 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T Nishijima et al.: "Plasma orexin-A-like immunoreactivity in patients with sleep apnea hypopnea syndrome"Peptides. 24. 407-411 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K Takahashi et al.: "Suppression of cytokine-induced expression of adrenomedullin and endothelin-1 by dexamethasone in T98G human glioblastoma cells"Peptides. 24. 1053-1062 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K takahashi et al.: "Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II"Peptides. 24. 301-306 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K Takahashi et al.: "Hypothalamus and Neurohypophysis. In ; Endocrine Pathology : Differential Diagnosis and Molecular Advances"RV Lloyd, ed. Humana Press. 39-60 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kitamuro T et al.: "Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells"Journal of Biological Chemistry. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morita M et al.: "HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin"EMBO Journal. 22(5). 1134-1146 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Li Y et al.: "Decreased expression of adrenomedullin during adipocyte-differentiation of 3T3-L1 cells"Hypertension Research. 26(Suppl). S41-S44 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasumoto K-I et al.: "Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling"EMBO Journal. 21. 2703-2714 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saito H et al.: "Melanocyte-specific microphthalmia-associated transcription factor isoform activates its own gene promoter through physical interaction with lymphoid-enhancing factor 1"Journal of Biological Chemistry. 277. 28787-28794 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Udono T et al.: "Elevated immunoreactive-adrenomedullin levels in the aqueous humor of patients with uveitis and vitreoretinal disorders"Peptides. 23. 1865-1868 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitamuro K 他: "Differential expression of adrenomedullin and its receptor component, receptor activity modifying protein(RAMP)2 during hypoxia in cultured human neuroblastoma cells"Peptides. 22・11. 1795-1801 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Totsune K 他: "Role of urotensin II in patients on dialysis"Lancet. 358. 810-811 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakayama M 他: "Increased expression of heme oxygenase-1 and bilirubin accumulation in foam cells of rabbit atherosclerotic lesions"Arterioscler Thromb Vasc Biol. 21. 1373-1377 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Udono T 他: "Induction of adrenomedullin by hypoxia in cultured retinal pigment epithelial cells"Invest Ophthalmol Vis Sci. 42. 1080-1086 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi K 他: "Expression of urotensin II and urotensin II receptor mRNAs in various human tumor cell lines and secretion of urotensin II-like immunoreactivity by SW-13 adrenocortical carcinoma cells"Peptides. 22. 1175-1179 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kimura Y 他: "Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart"J Clin Endocrinol Metab. 87. 340-346 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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