2007 Fiscal Year Final Research Report Summary
Effect of sialylation on leukocyte transmigration through endothelial cells
| Project/Area Number |
18570141
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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 |
Functional biochemistry
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
SHINOBU Kitazume The Institute of Physical and Chemical Research, Disease Glycomics, Deputy Laboratory Head (80301753)
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| Project Period (FY) |
2006 – 2007
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| Keywords | endothelial cell / sialyltransferase / apoptosis / BACE1 |
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| Research Abstract |
We wanted to know how sialylation deficiency would affect on the phenotype of endothelial cells. To do so, we prepared liver sinudoidal endothelial cells (LSECs) from wild type and ST6Ga1 I defieicnt mice. After collagenase perfusion, liver was isolated and cut into small pieces. LSECs were then separated by magnetic beads. We found that cell surface level of particular cell adhesion molecule was significantly decreased in LSECs from ST6Ga1 I deficient mice. We did cell surface biotinylation experiment and showed that half life of cell surface adhesion molecule was decreased. Interestingly, sislylateion deficient cells were more sensitive to mitochondrial-dependent apoptotic stimuli.
We elucidate the biological significance of ST6Gal I cleavage by BACE1. By BACE1 over-expression, sialylation of soluble glycoproteins (e.g. transferrin) were significantly increased (J. Biol. Chem. 282, 34896-34903). During hepatic acute reaction, liver produces a large amount of plasma glycoproteins, most of which are sialylated. Non-sialylated glycoproteins are trapped by asialoglycoprotein receptor in livers for degradation. Our current hypotheis is that plasma glycoproteins are effectively sialylated by soluble sialyltransferases by BACE1 over-expression. Our finding shed light on the functional siginificance of the cleavage-secretion of glycosyltransferase.
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[Book] ファルマシア2007
Author(s)
北爪しのぶ
Total Pages
5
Publisher
可溶型糖転移酵素:肝疾患バイオマーカーへの応用
Description
「研究成果報告書概要(和文)」より
