| Project/Area Number |
11670360
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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 |
Public health/Health science
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| Research Institution | Hirosaki University |
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Principal Investigator |
SATOH Kei Hirosaki University School of Medicine, Professor, 医学部, 教授 (20125438)
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| Co-Investigator(Kenkyū-buntansha) |
IMAIZUMI Tadaatsu Hirosaki University School of Medicine, Instructor, 医学部, 助手 (90232602)
YOSHIDA Hidemi Hirosaki University School of Medicine, Assistant Professor, 医学部, 講師 (40201008)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | platelet-activating factor (PAF) / PAF acetylhydrolase / oxidized phospholipid / PAF acetylhydrolase deficiency / vascular diseases / cancer / 喫煙 / 血小板活性化因子アセチルヒドロラーゼ / 動脈硬化 |
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| Research Abstract |
Platelet-activating factor (PAF) is a bioactive phospholipid that has agonistic activities towards many types of cells such as white blood cells, smooth muscle cells, and neuronal cells ; and it is implicated various pathological conditions. Oxidation of ether phospholipids results in the generation of derivatives with a sn-2 short chain residue, and such derivatives also acquire PAF-like bioactivities. PAF or PAD-like lipids are inactivated by PAF acetylhydrolase (PAF-AH), and a high level of activity is found in plasma. Plasma PAF-AH deficiency is due to a missense mutation in the gene (G994T) and its prevalence among a general Japanese population is reported to be about 4%. This mutation is also known to be a genetic risk factor of stroke or ischemic heart disease.
In the present study, we first found that the prevalence of plasma PAF-AH deficiency is virtually the same between healthy habitual smokers and non-smokers. There was no significant difference in the prevalence of the mutant gene between the group of the subjects who have risk factors for vascular diseases such as hypertension, diabetes mellitus, or hyperlipidemia (risk factor group) as compared to the group without such risk factors (normal group). However, among the subjects with normal genotype, the risk factor group had higher PAF-AH activity than the normal group. Such a difference was not observed for the subjects with the heterozygous genotype. Secondly, we detected an aggregating activity in lipid extracts of plasma obtained shortly after smoking cigarettes, and such activity co-migrated with authentic PAF in thin-layer chromatography.
We conclude that plasma PAF-AH is increased in various diseases, including chronic lifestyle diseases, as an adoptive mechanism and the deficiency of this enzyme may be associated with enhanced risk for the diseases.
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