| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
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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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