2006 Fiscal Year Final Research Report Summary
Protective role of blood PAF-acetylhydrolases against oxidation of lipids
| Project/Area Number |
17590069
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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 |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
KARASAWA Ken Teikyo University, Faculty of pharmaceutical sciences, Professor, 薬学部, 教授 (50186029)
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| Project Period (FY) |
2005 – 2006
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| Keywords | PAF / PAF-acetylhydrolases / Mass spectrometry / Oxidized lipids / LDL / Red blood cells |
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| Research Abstract |
Plasma PAF-acetylhydrolase (PAF-AH) preferentially hydrolyzes phosphatidylcholines with ω-carboxyl and ω-aldehydic short fatty acyl chains at the sn-2 position. Since these phospholipids are generated by non-enzymatic radical mediated oxidation, this LDL-associated enzyme is hypothesized to play a protective role in removal of pro-inflammatory phospholipids generated by oxidation of LDL particles. On the other hand, a loss-of-function mutation (Val279Phe) is found in 4% of Japanese populations and epidemiological studies suggest that this mutation is a risk factor for atherosclerotic diseases related to oxidative stress. In this study, we examined if accumulation of oxidized phosphatidylcholines is caused in the subjects with Val279Phe mutation by ESI-MS/MS analysis. When the LDL was treated with 5μM of Cu^<2+> for 3 h, 16:0-18:2 (+O), 18:0-18:2 (+P), 16:0-18:2 (+2O) and 18:0-18:2 (+2O) were accumulated in the LDL from the subject with this mutation. In addition, 16:0-18:2 (+O), 18:0-18:2 (+O) and 16:0-18:2 (+2O) were detected by incubating the LDL without Cu^<2+> for 16 h. By contrast, these oxidized phospholipids were not detected, when the LDL from the subjects with normal plasma PAF-AH activity was treated with Cu^<2>+. Furthermore, when the LDL from the subjects with normal PAF-AH enzyme activity was treated with DFP, the amounts of these oxidized phosphatidylcholines, which were accumulated in the LDL from the subjects with PAF-AH deficiency, were significantly increased. These results suggest that phosphatidylcholines with hydroxyl and hydroperoxyl long fatty acyl chains are one of the physiological substrates for this enzyme and this enzyme might play a role in degradation of these oxidized phospholipids.
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[Journal Article] Local expression of platlet-activating factor-acetylydrolase reduces accumulation of oxidized lipoproteins and inhibits inflammation, shear stress-induced thrombosis, and neointima formation in balloon-injured carotid arteries in nonhyperlipidemic rabbits2005
Author(s)
Hideki Arakawa, Jian-Yong Qian, Dolgor Baatar, Ken Karasawa, Yujiro Asada, Yasuyuki Sasaguri, Elizabeth R. Miller, Joseph L. Wiztum, Hikaru Ueno
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Journal Title
Circulation. 111
Pages: 3302-3309
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Adenovirus-mediated gene transfer and lipoprotein-mediated protein delivery of plasma PAF-AH ameliorates proteinuria in rat model of glomerulosclerosis.2005
Author(s)
Naoyuki Iso-O, Hiroshi Noto, Masumi Hara, Masako Togo, Ken Karasawa, Noriko Ohashi, Eisei Noiri, Yoshiaki Hashimoto, Takashi Kadowaki, Satoshi Kimura, Tsuyoshi Watanabe, Kazuhisa Tsukamoto
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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