1995 Fiscal Year Final Research Report Summary
Metabolic Changes of Sphingolipids associated with Regulation of Cell Growth and Differntiation
| Project/Area Number |
05671847
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | TEIKYO UNIVERSITY |
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Principal Investigator |
NOJIRI Hisao Teikyo Univ., Fuc.of Pharmaceuticl Sco., Associate Prof., 薬学部, 助教授 (70180742)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Sphingolipid / ganglioside / ceramide / Signal transduction / Cell differentiation / Growth regulation / Sphingomyelin |
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| Research Abstract |
Glycosphinogolipids (GSLs) , especially certain gangliosides, have recently been reported to participate in essential biological processes. Shpingosine derivatives, including cearmides, which are considered as breakdown products of GSLs and sphingomyelin (SM) , have also been demonstrated to modulate a variety of biological events, leading to the hypothesis that SM might be degraded and generate ceramides in response to various cellular stimuli, and may thus be involved in a novel signal transduction system without any consideration of the possible role of GSLs, even thogh both GSLs and SM contain ceramide. In the present study, we first established a simple method which enable simultaneous analysis of GSLs and SM of cultured cells. Early changes in sphingolipid metabolism, including GSLs and SM,during the macrophage-like differentiation of HL-60 cells were then analyzed to estimate the physiological significance of sphingolipids in the differentiation process.
The ceramide components of both GSLs and SM in HL-60 cells were identical. However, the molecular species of the ceramides preferentially used in biosynthesis were quite different in GSLs and SM.When HL-60 cells were stimulated to differentiate into macrophage-like cells by phorbol ester, marked changes in the metabolisof ceramide residues were observed in GSL,showing the activation of a biosynthetic pathways of ganglioside G_<M3>. No significant changes were, however, observed in the ceramide residue of SM.These results indicate that it is necessary to consider the overall metabolism of ceramides, including their origin, when investigating the functions of ceramides in signal transduction systems.
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[Publications] Yokoyama, K., Nojiri, H., Suzuki, M., Setaka, H., Suzuki, A.Nojima, S.: "Clear differences in ceramide metabolism between glyosplingolipids and sphingomyelin in a human promyelocytic leukemia cell line HL-60 stimulated by a differentiation inducer" FEBS Letters'. 368. 477-480 (1995)
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