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The investigation of the anti-apoptotic mechanism of lipocalin-type prostaglandin D synthase

Research Project

Project/Area Number 13670801
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionOsaka University

Principal Investigator

TANIIKE Masako  Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (30263289)

Co-Investigator(Kenkyū-buntansha) SHIMONO Kuriko  Osaka University Hospital, Medical Staff, 医学部附属病院, 医員(臨床研究)
MOHRI Ikuko  Osaka University Hospital, Medical Staff, 医学部附属病院, 医員(臨床研究)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordsprostaglandin D_2 / L-PGDS / twitcher / oligodendrocyte / demyelination / HPGDS / apoptosis / ニューロングリア相関 / twitcher
Research Abstract

The genetic demyelinating mouse twitcher is a model of the human globoid cell leukodystrophy, caused by galactosylceramidase deficiency. Lipocalin-type prostaglandin (PG) D synthase (L-PGDS), a protein expressed in mature oligodendrocytes(Ols), was progressively upregulated in twitcher Ols; whereas expression of OL-associated proteins was downregulated during demyelination in twitcher brains. The upregulation of L-PGDS was more remarkable in perineuronal Ols than in interfascicular Ols. A larger number of L-PGDS-positive Ols was found in selected fiber tracts of twitcher brains where fewer apoptotic cells were detected. Mice doubly deficient for L-PGDS and GALC disclosed a large number of apoptotic neurons, which were never seen in twitcher brains, in addition to an increased number of apoptotic Ols. A linear positive correlation was observed between the population of L-PGDS-posiuve Ols in the twitcher brain and the ratio of apoptotic nuclei in the double mutant versus those in the twitcher, suggesting a dose-dependent effect of L-PGDS against apoptosis. These lines of evidence suggest that L-PGDS is an anti-apoptotic molecule protecting neurons and Ols from apoptosis in the twitcher mouse. In addition, we disclosed that hematopoietic PGDS (HPGDS), the isozyme of L-PGDS, was also upregulated in activated microglia, accompanied with induced expression of PGD receptor in the neighboring hypertrophic astrocytes. The level of PGD_2 increased ten-fold in the twitcher brains compared with those of normal controls and its level was similarly high in the L-PGDS-deficient twitcher. Taken together, we currently suppose that 1) HPGDS, not LPGDS, is mainly responsible of the production of PGD_2 in the twitcher brains and that 2) the anti-apoptotic effect of L-PGDS is not due to the production of PGD_2 but to its function as a lipocalin.

Report

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

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Taniike M, Mohri I, et al.: "Perineuronal Oligodendrocytes Protect against Neuronal Apoptosis through the Production of Lipocalin-Type Prostaglandin D Synthase in a Genetic Demyelinating Model"J Neurosci. 22(12). 4885-4896 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okinaga T, Mohri I, et al.: "Induction of hematopoietic prostaglandin D synthase in hyalinated necrotic muscle fibers : its implication in grouped necrosis"Acta Neuropathol. 104. 377-384 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mohri I, Eguchi N, et al.: "Hematopoietic prostaglandin D synthase is expressed in microglia in the developing postnatal mouse brain"Glia. 42. 263-274 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] taniike M, Mohri I, et al.: "Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model."J Neurosci. 22(12). 4885-4896 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okinaga T, Mohri I, et al.: "Induction of hematopoietic prostaglandin D synthase in hyalinated necrotic muscle fibers: its implication in grouped necrosis."Acta Neuropathol. 104. 377-384 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mohri I, Eguchi N, et al.: "Hematopoietic prostaglandin D synthase is expressed in microglia in developing postnatal mouse brains."Glia. 42. 263-274 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] "Drug design"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Taniike M, Mohri I, et al.: "Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model"J Neurosci. 22(12). 4885-4896 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okinaga T, Mohri I, et al.: "Induction of hematopoietic prostaglandin D synthase in hyalinated necrotic muscle fibers : its implication in grouped necrosis"Acta Neuropathol. 104. 377-384 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mohri I, Eguchi N, et al.: "Hematopoietic prostaglandin D synthase is expressed in microglia in the developing postnatal mouse brain"Glia. (In press). (2003)

    • Related Report
      2002 Annual Research Report

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

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