| Project/Area Number |
06454657
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | FACULTY OF AGRICULTURE |
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Principal Investigator |
ITO Makoto INSTTIUTION KYUSHU UNIVERSITY DEPARTMENT AGRICULTURE TTILE OF POSTTION ASSOCIATEPROFESSOR, 農学部, 助教授 (40253512)
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| Co-Investigator(Kenkyū-buntansha) |
HIGASHI Hideyoshi INSTTIUTION MITSUBISHIKASEI OF LIFESCIENCES TTILE OF POSTTION SENIOR RESEARCHER, 主任研究員
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Ganglioside / Endogly coceramidase / Glycolipid / Ceramide / Neuron / Cam kII / Calmodulin / GMI / エンドグリコセラミダーゼ / CaM KII / 棟脂質 / 棟鎖生物学 / EGF受容体 |
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| Research Abstract |
This report describes the homeostasis of glycosphingolipid (GSL) on the cell surface as revealed for the first time by an application of endoglycoceramidase (EGCase) capable of hydrolyzing the linkage between the oligosaccharide and the ceramide of various GSLs. When cell-surface GSLs of B16 melanoma cells were hydrolyzed by the action of EGCase, the synthesis of GSLs was found to increase transiently, possibly due to the activation of UDP-glucose : ceramide glucosyltransferase. As a result, the cell-surface GSL content was restored quickly to exactly the same level found without the EGCase treatment, if EGCase was removed from the cell culture. Treatment of erythrocytes with EGCase was found to increase the ceramide content of the plasma membrane. Surprisingly, however, in B16 cells the increase of membrane ceramide by EGCase caused the suppression of de novo ceramide production, resulting in maintenance of the ceramide content of B16 cells at the same level even after EGCase treatment. The signal for homeostatic regulation could be the ceramide released by the action of EGCase, since C_2-ceramide was found to mimic in part the action of EGCase ; it suppressed de novo production of ceramide and was directly converted to C_2-ceramide GM3. Our finding demonstrates a novel form of homeostatic regulation coupled to the GSL-synthesizing system in mammalian cells for maintaining the contents of both cell-surface GSLs and free ceramide. Since many opportunistic pathogens were found to produce EGCase extracellularly, this restoration mechaniam could also be present as a defense mechanism against microbial EGCase.
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