| Project/Area Number |
08671193
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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 |
内分泌・代謝学
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| Research Institution | KURUME UNIVERSITY |
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Principal Investigator |
KAMIDO Hiroshi KURUME UIV,SCHOOL OF MEDICINE,ASSISTANT PRO, 医学部, 講師 (30248455)
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| Co-Investigator(Kenkyū-buntansha) |
SHOJI Shingo KURUME UIV,SCHOOL OF MEDICINE,LECTURER, 医学部, 助手 (10281528)
HAYASHI Hideki KURUME UIV,SCHOOL OF MEDICINE,LECTURER, 医学部, 助手 (50238119)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | ARTERIOSCLEROSIS / PEROXIDATION / CORE ALDEHYDE / PLATELET-ACTIVATING FACTOR / PLATELET / THROMBOSIS / ACUTE CORONARY SYNDROME |
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| Research Abstract |
In previous studies we isolated short-chain (C5 and C9) aldehyde-containing acyl GPC as secondary products of lipid peroxidation from oxidized LDL (J Lipid Res 36 : 1876) and human atheromas (Circulation 94 : I-707). In subsequent studies we have recognized that in atheromas much of the short-chain aldehyde is bound to sn-1-alkyl GPC.In the present study we have synthesized the sn-1-alkyl GPC core aldehyde and have demonstrated its platelet aggregating activity via the platelet-activating factor (PAF) receptor (Atherosclerosis 134 : 183).
Specifically, 1-O-hexadecyl 2- (5-oxovaleroyl) -sn-GPC (C5CHO Alkyl GPC) and 1-palmitoyl-2- (5-oxovaleroyl) -sn GPC (C5CHO Acyl GPC) were semi-synthesized using reductive ozonolysis. The core aldehydes in human atheromas were identified by high performance liquind chromatography with on-line electrospray mass spectrometry.
C5CHO Alkyl GPC induced aggregation of washed rabbit platelets (ED50 approximately 50 nM). In contrast, C5CHO Acyl GPC induced shape change, but did not induce aggregation, confirming the importance of sn-1-alkyl ether group in the GPC.Aggregations by C5CHO Alkyl GPC were inhibited by two different PAF receptor antagonists (CV-6209 and BN52021).
The C5CHO hexadecyl GPC is derived mainly from 1-O-hexadecyl-2-arachidonoyl-sn-GPC that is present in atheroma and shown to be a precursor of eicosanoids and PAF.These lipids are reported to have specific effects on platelets and blood vessels and have been established as lipid mediators of inflammation. Taken together, our results suggest that Alkyl GPC core aldehydes present in atheroma could be involved in the development of acute events, in which thrombus formation following plaque disruption plays an important role.
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