| Project/Area Number |
09470509
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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 | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | KOBE PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
SUGAHARA Kazuyuki Dept.of Biochemistry, KOBE PHARMACEUTICAL UNIVERSITY Professor, 薬学部, 教授 (60154449)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Shuhei Dept.of Biochemistry, KOBE PHARMACEUTICAL UNIVERSITY Lecturer, 薬学部, 講師 (70240017)
KITAGAWA Hiroshi Dept.of Biochemistry, KOBE PHARMACEUTICAL UNIVERSITY Assistant Professor, 薬学部, 助教授 (40221915)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | chondroitin sulfate / glycosaminoglycan / heparan sulfate / tumor suppressor / EXT gene family / neurite outgrowth / angiogenesis / glycosyltransferase / コンドロイチン硫酸E / アンジオモジュリン / ミッドカイン / プロテオグリカン / シンデカン / ヘパリン / N-アセチルグルコサミン / グルクロン酸転移酵素 / コンドロイチン / ヘバラン硫酸 / EXT / 硫酸化オリゴ糖 / フォリスタチン |
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| Research Abstract |
1) The so-called D disaccharide unit was demonstrated in the chondroitin sulfate preparation purified from neonatal mouse brains. Neurite outgrowth promoting activity was also demonstrated for the commercial shark cartilage chondroitin sulfate D preparation which contained a high proportion of the D disaccharide unit.
2) It was demonstrated that the commercial squid cartilage chondroitin sulfate E preparation had neurite outgrowth promoting activity toward cultured neuronal cells derived from embryonic rat brains. The chondroitin sulfate E preparation was further demonstrated to bind midkine and inhibit the midkine-mediated neuronal cell adhesion to the culture substrate.
3) The tumor-derived adhesion factor, angiomodulin, promotes the cord formation towards the cultured human tumor cell line ECV304, and has been proposed to be associated with tumor angiogenesis. The angiomodulin-binding domain on heparan sulfate chains was shown to be larger than dodecasaccharides and highly sulfated.
4) Sulfation of the chondroitin sulfate chains and sulfotransferase activities in embryonic chick brains were shown to be regulated during embryonic development and neonatal growth.
5) Glucuronyltransferase that is involved in the synthesis of the glycosaminoglycan-protein linkage region tetrasaccharide sequence, GlcA-Gal-Gal-Xyl, was molecularly cloned and its properties were characterized.
6) A truncated tetrasaccharide fragment, GlcA-Gal-Gal-Xyl, which corresponded to the glycosaminoglycan-protein linkage region, was demonstrated on a part-time proteoglycan, α-thrombomodulin.
7) α-GalNAc transferase purified from the culture medium of a human sarcoma cell line was shown to be identical with the EXTL2 protein encoded by the EXTL2 gene, which belonged to the tumor suppressor EXT gene family, and to harbor the α-GlcNAc transferase activity that initiates and determines the heparan sulfate synthesis.
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