Project/Area Number |
18509001
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Eating habits, studies on eating habits
|
Research Institution | University of Shizuoka |
Principal Investigator |
OHSHIMA Hiroshi University of Shizuoka, Department of Food and Nutritional Sciences, Professor (80433209)
|
Co-Investigator(Kenkyū-buntansha) |
MASUDA Shuichi University of Shizuoka, Department of Food and Nutritional Sciences, Assistant Professor (40336657)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,390,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | cholesterol / reactive oxygen and nitrogen species / metabolic syndrome / chronic inflammation / ozone |
Research Abstract |
The metabolic syndrome is a risk factor for atherosclerosis. Adipocytokines produced by fat cells may activate various inflammatory cells to produce reactive oxygen and nitrogen species, which play important roles in host defenses against pathogens as well as in tissue damage in inflamed tissues. It has recently been reported that human activated neutrophils produce an ozone-like oxidant (s) in vivo, but conflicting experimental results have also been reported. In the present study in order to establish whether human inflammatory cells produce the ozone-like oxidant in vivo, we have investigated the followings using atheronal-A and B, which are oxidized-cholesterols specifically produced by the reaction with ozone: (1) synthesis and characterization of atheronal-A and B, (2) development of a highly sensitive and specific method to detect atheronal-A and B using fluorescent dansyl hydrazine derivatives, (3) elucidation of the mechanism for the formation of atheronal-A and B and also ozo
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ne-like oxidant (s) in vivo by inflammatory cells, (4) biological activities, especially ability to induce apoptotic cell death, and(5)detection of atheronal-A and B in tissues such as the liver of diabetes rats. Our developed method is about one thousand times more sensitive than the previously reported methods and can detect fmol levels of the compounds easily. Using this method, we have shown that increased levels of atheronal-B were formed in human neutrophil-like (HL-60) cells activated with phorbolester, compared to those without activation. As the formation of atheronal-B was inhibited specifically by a compound which inhibits ozone-mediated oxidation, our data strongly suggest that ozone produced by the activated HL-60 is involved in the formation of atheronals. It was also shown that atheronals exhibited strong cytotoxicity. As we also detected elevated levels of atheronals in the liver of diabetes rats, the compounds could be measured as a novel marker for the metabolic syndrome. Less
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