| Project/Area Number |
13557016
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
EGUCHI Naomi Osaka Bioscience Institute, 2nd Department, Vice-Head, 第2研究部, 研究副部長 (10250086)
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| Co-Investigator(Kenkyū-buntansha) |
URADE Yoshihiro Osaka Bioscience Institute, 2nd Department, Head, 第2研究部, 研究部長 (10201360)
SAKATA Mie Osaka Bioscience Institute, 2nd Department, Research Collaborator, 第2研究部, 研究員 (10353525)
曲 衛敏 財団法人大阪バイオサイエンス研究所, 第2研究部・日本学術振興会, 外国人特別研究員
INOUE Teruo Koshigaya Hospital Dokkyo University School of Medicine, Department of Cardiology, Lecture, 越谷病院, 循環器内科・講師 (20168454)
EGUCHI Yutaka Shiga University of Medical Science, Intensive Care Unit, Lecture, 医学部, 講師 (00263054)
QU Wei-Min Osaka Bioscience Institute, 2nd Department, Japan Society for the Promotion of Science, Postdoctoral Fellowship for Foreign Researcher
黄 志力 財団法人大阪バイオサイエンス研究所, 第2研究部, 日本学術振興会外国人特別研究員 (10321704)
竹之下 真 滋賀医科大学, 医学部, 助教授 (00144486)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2001: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | prostaglandin D synthase / prostaglandin D_2 / gene-manipulated mice / animal model for human disease / sleep disorders / atherosclerosis / diabetes mellitus / obesity / アレルギー |
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| Research Abstract |
We investigated the involvement of prostaglandin (PG) D_2 an its metabolites in diseases generated by our life style and their association with sleep disorders. We found the following evidences: (1) lipocalin-type PGD synthase (L-PGDS) was a secretory glycoprotein with, different sugar chains depending on the tissues and was excreted into various body fluids, such as the cerebrospinal fluid, peripheral blood, and urine. (2) The arterial level of L-PGDS increased in proportion to severity of human coronary artery disease and the increased L-PGDS was produced most likely by proliferating smooth muscle cells in the atheromatous coronary arteries. Therefore, serum L-PGDS may be a sensitive bio-marker for coronary atherosclerosis. (3) Urinary L-PGDS excretion was significantly increased in patients with diabetic nephropathy, IgA nephropathy, and chronic glomerulonephritis even when serum creatinine was not increased. Thus, urinary L-PGDS is useful to detect less advanced stages of renal dis
… More
eases. (4) In the central nervous system, L-PGDS was produced in the leptomeninges, choroid plexus, and oligodendrocytes (OLs), whereas DP receptor (DPR), one of PGD_2 receptor, was dominantly localized in the leptomeninges of the basal forebrain. PGD_2-induced sleep and the increase in extracellular adenosine concentration were not observed in DPR-deficient mice, indicating that PGD_2-induced sleep is mediated by DPR and adenosine. (5) L-PGDS- and DPR-deficient mice showed no rebound of non-rapid eye movement (NREM) sleep after sleep deprivation, suggesting that PGD_2 is involved in the NREM sleep homeostasis after prolonged wakefulness. (6) The mRNA for L-PGDS was upregulated in OLs during a progressive demyelination in Twitcher mice, an animal model of human Krabbe disease. L-PGDS-deficient Twitcher mice exhibited a remarkable increase in number of apoptotic OLs and neurons during a progressive demyelination, suggesting that L-PGDS in OLs can protect against apoptosis of OLs and neurons by demyelination. Less
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