Study of the regulation mechanism of cell adhesion caused by a nobel modification of sialic acid
| Project/Area Number |
14580636
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
KANAMORI Akiko Aichi Cancer Center, Division of Molecular Pathology, Researcher, 分子病態学部, 研究員 (00261173)
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| Co-Investigator(Kenkyū-buntansha) |
KANNAGI Reiji Aichi Cancer Center, Division of Molecular Pathology, Chief., 分子病態学部, 部長 (80161389)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | sialic acid / cell adhesion / selectin / cDNA cloning |
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| Research Abstract |
There are many reports indicating that the reactivity of adhesion molecules with sialoglycoconjugates is due to their recognition of the carboxyl group of sialic acid. Recently we found a novel metabolic pathway to modify the sialic acid to be a novel ring form named "cyclic sialic acid", lacking its carboxyl group. This modification should regulate the strength of cell adhesion mediated by sialic acid. In this study, we tried to investigate the mechanism of regulation of cell adhesion by isolation of a cDNA encoding an enzyme named sialic acid cyclase, which catalyzes above modification.
In the process of the expression cloning of the sialic acid cyclase cDNA, we obtained a cDNA clone encoding human interferon-gamma as a factor that enhances the expression of cyclic sialyl 6-sulfo Lewis x. The expression of cyclic sialyl 6-sulfo Lewis x was observed in time-and dose-dependent manner, when the sialyl 6-sulfo Lewis x expressing cells were treated with interferon-gamma. These effects were reversible and detected on human lymphoid cells more rapidly than on cells derived from epithelial cells. This is the first report to identify the naturally occurring factor which can induce the expression of cyclic sialic acid. Investigation of the mechanism induced by interferon-gamma to express cyclic sialyl 6-sulfo Lewis x will clarify the function of this metabolic pathway.
In the other hand, the cell lines such as YT or HUT-102 stained positively by monoclonal antibody (mAb) G159, which recognizes cyclic silayl 6-sulfo Lewis x antigen, are not stained positively with the mAbs recognizing precursor of cyclic silayl 6-sulfo Lewis x. We examined the intracellular staining pattern of the fixed and permeabilized cells and detected the precursor sialoglycoconjugates in vehicles in cell coat region. It is suggested that some formation of cyclic sialic acid is occurred in cell coat region.
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Report
(3 results)
Research Products
(15 results)
