| Project/Area Number |
08557015
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 University |
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Principal Investigator |
TANIGUCHI Naoyuki Osaka University Medical School, Professor, 医学部, 教授 (90002188)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Makoto KIRIN BREWERY Co., Ltd Central Laboratories For Key Technology, Team Leader, 基盤研究所, 主任研究員
CHUNG Mun Ok (IKEDA Yoshi) Osaka University Medical School, Assistant Professor, 医学部, 助手 (60252657)
井原 義人 大阪大学, 医学部, 助手 (70263241)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥17,700,000 (Direct Cost: ¥17,700,000)
Fiscal Year 1997: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1996: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | glycosyltransferase / glycoprotein / glycogene / digosaccharide / remodeling / gnt3 / 糖鎖 / 肝癌 / 遺伝子発現 |
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| Research Abstract |
N-Acetylglucosaminyltransferase-III (GnT-III) catalyzes the formation of bisecting N-acetylglucosamine (GlcNAc) in the biosynthesis of N-linked oligosaccharides. To examine the effect of biosecting GlcNAc on the natural killer (NK) cytotoxicity, the GnT-III gene was introduced into NK-sensitive K562 cells that have no detectable GnTIII activity. Introduction of the gene resulted in complete blockage of the NK cytotoxicity against the transfected cells and also in a decrease of the binding of the effector cells to the target cells. After s.c. injection into nude mice, GnT-III-transfectants produced spleen colonization, although no spleen lesions were formed by control cells. In nude mice depleted of NK cells by anti-asialo GM1 antibody, both transfectants and controls yielded spleen colonization equally. These results indicate that K562 cells expressing GnT-III are resistant to NK cytotoxicity, resulting in spleen colonization in nude mice.
The functional consequence of the sugar chain remodeling was examined in rat pheochromocytoma (PC12) cells by transfection of GnT-III gene. Nerve growth factor (NGF) stimulates neurite outgrowth for differentiation in PC12 cells, and the stimulation is mediated by a glycoprotein receptor for NGF,Trk. Transfection of GnT-III gene lead to loss of changes in morphology and growth rate upon NGF treatment. The detailed studies revealed that the altered structure of sugar chain in Trk impaired dimerization and phosphorylation of the receptor. These suggest that the function of glycoprotein receptor such as Trk is modified by alteration of N-glycan structure.
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