Identification of inflammation-mediated oxidized cholesterols as novel biomarkers of the metabolic syndrome
| Project/Area Number |
18509001
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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 |
Eating habits, studies on eating habits
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| Research Institution | University of Shizuoka |
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Principal Investigator |
OHSHIMA Hiroshi University of Shizuoka, Department of Food and Nutritional Sciences, Professor (80433209)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Shuichi University of Shizuoka, Department of Food and Nutritional Sciences, Assistant Professor (40336657)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| 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)
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| Keywords | cholesterol / reactive oxygen and nitrogen species / metabolic syndrome / chronic inflammation / ozone |
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| 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
… More
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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Report
(3 results)
Research Products
(53 results)
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[Journal Article] Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters.2008
Author(s)
Sawa, T., Mounawar, M., Tatemichi, M., Gilibert, I., Katoh, T. & Ohshima, H.
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Journal Title
Cancer Letters (in press)
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Peer Reviewed
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[Journal Article] Geographic Distribution of Liver and Stomach Cancers in Thailand in Relation to Estimated Dietary Intake of Nitrate, Nitrite, and Nitrosodimethylamine.2008
Author(s)
E. J. Mitacek, K. D. Brunnemann, M. Suttajit, L. S. Caplan, C. E. Gagna, K. Bhothisuwan, S. Siriamornpun, C. F. Hummel, H. Ohshima, R. Roy, and N. Martin
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Journal Title
Nutrition and Cancer 60
Pages: 196-203
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Peer Reviewed
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[Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of aforeign body accelerate sarcoma development in Trp53+/- mice2007
Author(s)
Tazawa, H., Tatemichi, M., Sawa, T., Gilibert, I., Ma, N., Hiraku, Y., Donehower, L. A., Ohgaki, H., Kawanishi, S.&Ohshima, H
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Journal Title
Carcinogenesis. 28(1)
Pages: 191-198
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Peer Reviewed
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[Presentation] Cholesterol ozonolysis products as a possible biomarker for metabolic syndrome2008
Author(s)
Tomono, S., Iwabuchi, T., Yasue, Y., Niizuma, S., Miyoshi, M., Ohshima, H
Organizer
International symposium on Biomarkers of Oxidative Stress in Health and Diseases
Place of Presentation
Osaka,Japan
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] ozonolysis products as a possible biomarker for metabolic syndrome2008
Author(s)
Tomono, S., Iwabuchi, T., Yasue, Y., Niizuma, S., Miyoshi, M., Ohshima, H
Organizer
International symposium on Biomarkers of Oxidative Stress in Health and Diseases
Place of Presentation
(Osaka, Japan), Jan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] オゾン酸化コレステロールによるHレ60細胞の細胞傷害分子機構2007
Author(s)
伴野 勧, 新妻 聖子, 岩渕 智恵, 安江 祐佳里, 三好 規之, 大島 寛史
Organizer
第80回日本生化学会大会(Biochemistry and Molecular Biology2007)
Place of Presentation
横浜市(パシフィコ横浜)
Year and Date
2007-12-11
Description
「研究成果報告書概要(和文)」より
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[Presentation] Helicobacter pylori Infection,Oxidative and Nitrative Stress and Stomach Cencer2007
Author(s)
Ohshima H., Sawa, T.Tatemichi, M., Bancel, B., Pignatelli, B
Organizer
The Keystone Symposium on 'Frontiers in Gastrointestinal Cancer:Molecular Genetics, Inflammation, Early Detection and Therapy'
Place of Presentation
Beijing,China
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] Molecular mechanism of cell damage by ozonolysis of cholesterol in HL-60 cells2007
Author(s)
Tomono, S., Niiduma, S., Iwabuchi, T., Yasue, Y., Miyoshi, N., Ohshima, H
Organizer
Biochemistry and Molecular Biology 2007
Place of Presentation
Yokohama
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Helicobacter pylori Infection, Oxidative and Nitrative Stress and Stomach Cancer2007
Author(s)
Ohshima, H., Sawa, T., Tatemichi, M., Bancel, B., Pignatelli, B
Organizer
Invited speaker at the Keystone Symposium on `Frontiers in Gastrointestinal Cancer: Molecular Genetics, Inflammation, Early Detection and Therapy'
Place of Presentation
Beijing, China
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Book] Inflammation Induced Carcinogenesis and Chemoprevention2008
Author(s)
Ohshima, H., Tomono, S., Lai, Y-L., Miyoshi, N
Publisher
Knasmuller,S.DeMarini,D.M.,Johnson,IT.& Gerhauser(In press)
Description
「研究成果報告書概要(和文)」より
Related Report
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