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Heme oxygenase in the brain

Research Project

Project/Area Number 09670117
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TAKAHASHI Kazuhiro  Tohoku University, School of Medicine, Associate Professor, 医学部, 助教授 (80241628)

Co-Investigator(Kenkyū-buntansha) SHIBAHARA Shigeki  Tohoku University, School of Medicine, Professor, 医学部, 教授 (70206142)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsHeme oxygenase / Brain / Nitric Oxide / Carbon monoxide / Adrenomedullin / Hypoxia / Oxidative Stress / Glioblastoma / アドレナデュリン / heme Oxygenase / Nitric Oxide / NO / carbon monoxide / adrenomedullin / cytokine / glioblastoma / hypoxia
Research Abstract

Heme oxygenase is an essential enzyme in heme catabolism that cleaves heme to release carbon monoxide, iron and biliverdin. There are at least two types of heme oxygenase isozymes, inducible heme oxygenase-1 and constitutively expressed heme oxygenase-2. We have found that expression heme oxygenase-l is induced by NO donors, such as sodium nitroprusside, in variouskinds of cultured cells including human glioblastoma cells (T98G and A 172), human cervical cancer cells (HeLa), melanoma cells (MeWo) and colonic carcinoma cells (DLD)- 1). Transient transfection assays using DLD-1 cells revealed that heme oxygenase-1 induction by sodium nitroprusside was mediated by cadmium-responsive element and AP-1, which are located in the promoter region of human heme oxygenase-1 gene (about -4.0 kb). In addition, we showed that a(GT)n repeat in the human heme oxygenase-1 gene promotor region (about -200 b) is highly polymorphic. On the other hand, expression of heme oxygenase-1 mRNA was considerably suppressed by interferon-gamma in T98G cells, suggesting the presence of a regulatory system for heme oxygenase-l overexpression in the brain.
Adrenomedullin is a vasodilator peptide isolated from pheochromocytoma. Although adrenomedullin was initially reported to be absent in the brain, we showed that adrenomedullinand its mRNA were highly expressed in the human brain and pituitary. Adrenomedullin is produced by various kinds of tumors including glioblastoma, choroid plexus carcinoma and colonic carcinoma, suggesting that adrenomedullin is related to the growth and proliferation of tumor cells. Heme oxygenase-1 is known to be induced by hypoxia. We showed that adrenomedullin was also induced by hypoxia. This induction may be a defense reaction agaist hypoxia, because adrenomedullin has vasodilator and bronchodilator actions.

Report

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

    (31 results)

All Other

All Publications (31 results)

  • [Publications] E Hara et al.: "Induction of heme oxygenase-1 as a response in sensing the signals cvoked by distinct nitric oxide donors." Biochemical Pharmacolology. 印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Takahashi et al.: "Suppression of heme oxygenase-1 mRNA expression by interferon-γ in human glioblastoma cells." Journal of Neurochemistry. 印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Takahashi et al.: "Possible implications of the induction of human heme oxygenase-1 by nitric oxide donors." Journal of Biochemistry. 121. 1162-1168 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T Kimpara et al.: "Microsatellite polymorphism for a (GT)n repeat in the human heme oxygenase-1 gene promoter and its application studies with Alzheimer and Parkinson disease." Human Genetics. 100. 145-147 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M Nakayama et al.: "Induction of adrenomedullin by hypoxia and cobalt chloride in human colorectal carcinoma cells." Biochemical and Biophysical Research Communications. 243. 514-517 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Takahashi et al.: "Production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells." Journal of Neurochemistry. 68. 726-731 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Takahashi et al.: "Melanin concentrating hormone in human brain. In MCH and Seizures : Neuromolecular and Neuroendocrine Aspects" Research Signpost, Trivandrum, Indea., 87-95 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E Hara et al.: "Oxygen Homeostasis and Its Dynamics." Springer, Tokyo., 328-332 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E Hara, K Takahashi, K Takeda, M Nakayama, M Yoshizawa, H Fujita, K Shirato, S Shibahara: "Induction of heme oxygenase-1 as a response in sensing the signals cvoked by distinct nitric oxide donors." Biochem Pharmacol. (in press.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Takahashi, M Nakayama, K Takeda, H Fujita, S Shibahara: "Suppression of heme oxygenase-1 mRNA expression by interferon-gamma in human glioblastoma cells." J Neurochem. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Takahashi, E Hara, K Ogawa, D Kimura, H Fujita, S Shibahara: "Possible implications of the induction of human heme oxygenase-1 by nitric oxide donors." J Biochem. 121. 1162-1168 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T Kimpara, A Takeda, K Watanabe, Y Itoyama, S Ikawa, M Watanabe, H Arai, H Sasaki, S Higuchi, N Okita, S Takase, H Saito, K Takahashi, S Shibahara: "Microsatellite polymorphism for a (GT)_n repeat in the human heme oxygenase-1 gene promoter and its application studies with Alzheimer and Parkinson disease." Hum Genet. 100. 145-147 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M Nakayama, K Takahashi, O Murakami, K Shirato, S Shibahara: "Induction of adrenomedullin by hypoxia and cobalt chloride in human colorectal carcinoma cells." Biochem Biophys Res Commun. 243. 514-517 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Takahashi, F Satoh, E Hara, O Murakami, T Kumabe, T Tominaga, T Kayama, T Yoshimoto, S Shibahara: "Production and secretion of adrenomedullin by cultured choroid plexus carcinoma cells." J Neurochem. 68. 726-731 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K Takahashi, T Mouri, S Shibahara: "Melanin concentrating hormone in human brain." MCH and Seizures : Neuromolecular and Neuroendocrine Aspects.KM Knigge, A Prasad, S Pretel and Janet E Wagner eds.Research Signpost, Trivandrum, India.87-95 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E Hara, K Takahashi, H Fujita, S Shibahara: "Expression of heme oxygenase and inducible nitric oxide synthase mRNA in a human glioblastoma cell line." Oxygen Homeostasis and Its Dynamics.Keio University Symposia for Life Science and Medicine.Y Ishimura, H Shimada and M Suematsu eds.Springer, Tokyo.Volume 1. 328-332 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] E Hara et al: "Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors." Biochemical Pharmacolology. 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] K Takahashi et al.: "Suppression of heme oxygenase-1 mRNA expression by interferon-γ in human glioblastoma cells." Journal of Neurochemistry. 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] K Takahashi et al.: "Production and secretion of endothelin-1 by cultured choroid plexus carcinoma cells." Journal of Cardiovascular Pharmacology. 31 (Suppl.1). S367-S369 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H Suzuki et al.: "Role of neurofibromin in modulation of expression of the tyrosinase-related protein 2 gene." Journal of Biochemistry. 124. 992-998 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M Nakayama et al.: "Induction of adrenomedullin by hypoxia in cultured human coronary artery endothelial cells." Peptides. 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] K Takahashi et al.: "Production and secretion of neuropeptides by nervous system tumors." Cancer Journal. 11. 237-241 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S Shibahara et al.: "Genetic regulation of the pigment cell. In The Pigmentary System : Physiology and Pathophysiology." Oxford University Press, New York, Oxford., 251-273 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K Takahashi et al.: "Possible implications of the induction of human heme oxygenase-1 by nitric oxide donors." Journal of Biochemistry. 121. 1162-1168 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T Kimpara et al.: "Microsatellite polymorphism for a (GT)_n repcat in the human heme oxygenase-1 gene promoter and its application studies with Alzheimer and Parkinson descase." Human Genetics. 100. 145-147 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K Takahashi et al.: "Expression of adrenomedullin mRNA in the human brain and pituitary." Peptides. 18. 1051-1053 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K Takahashi et al.: "Production and secretion of adrenomedullin from glial cell tumors and its effects on cAMP production." Peptides. 18. 1117-1124 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M Nakayama et al.: "Induction of adrenomedullin by hypoxia and cobalt chloride in human colorectal carcinoma cells." Biochemical Biophysical Research Commununications. (印刷予定). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 高橋 和広他: "酸化ストレスとheme oxygenase" The Ling perspectives. 6. 74-78 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] E Hara et al.: "Oxygen Homeostasis and Its Dynamics.pp328-332" Springer,Tokyo.Y Ishimura,H Shimada and M Suematsu eds., 620 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K Takahashi et al.: "Neuroendocrine and Neuromolecular Aspects of Epilepsy and Related Brain Disorders." Research Signpost K M K nigge,S Pretel and A Prasad eds.(印刷予定), (1998)

    • Related Report
      1997 Annual Research Report

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

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