PHISIOLOGICAL ACTIVITY OF CERAMIDE AND RELATED SUBSTANCE
Project/Area Number |
07672357
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | HYOGO UNIVERSITY OF TEACHER EDUCATION |
Principal Investigator |
MASUZAWA Yasuo HYOGO UNIVERSITY OF TEACHER EDUCATION,PROFESSOR, 学校教育学部, 教授 (30119622)
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Project Period (FY) |
1995 – 1996
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Project Status |
Completed (Fiscal Year 1996)
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Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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Keywords | ceramide / cis-trans isomer / acetylene type / molecular species / quantification / apoptosis / docosahexaenoic acid / sphingosine / 新規定量法 |
Research Abstract |
1. A new method for quantitative analysis of ceramide molecular species was developed using fluorescence HPLC.This method was applied to quantification of free ceramide in HL60 and U937 cells. Total amount of free ceramide was 3.9 <plus-minus> 0.42 mug/108 cells and 2.6 <plus-minus> 0.43 mug/108 cells, respectively. This is the first quantitative analysis of molecular species of free ceramide in intact ce 2. The requirement of a trans double bond for the biological action of ceramide was assessed by comparing the apoptosis-inducing activity of various ceramide analogs. An acetylene type derivative (TRP-Cer) yielded the highest percentage of apoptotic cells corresponding to three times that induced by C6-Cer. C6-cis-Cer also showed stronger activity than C6-Cer. These observations suggest that the trans configuration of ceramide is not necessarily essential for the activity to induce apoptosis. In addition, distinctive activity of C6-TRP-Cer suggests that this ceramide analog might be useful for developing a new type of antitumor drug. 3. Effect of exogenously-added polyunsaturated fatty acids on the apoptosis of HL60 induced by cell-permeable ceramide or sphingosine. Ceramide-induced apoptosis was not affected by the preincubation with polyunsaturated fatty acids. However sphingosine-induced apoptosis was much attenuated by 24h incubation with DHA.These results indicated that the mechanism for the induction of apoptosis was different between ceramide and sphingosine, and that DHA may specifically reduce PKC inhibition-dependent apoptosis.
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Report
(3 results)
Research Products
(3 results)
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[Publications] Kishida, E., Kasahara, M., Takagi, Y., Matsumura, M., Hayashi, T., Kobayashi, S., and Masuzawa, Y.: "Evaluation of a trans configuration for the apoptosis-inducing activity of ceramide" J.Lipid Mediators and Cell Signal.(in press). (1997)
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