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2007 Fiscal Year Final Research Report Summary

Identification of inflammation-mediated oxidized cholesterols as novel biomarkers of the metabolic syndrome

Research Project

Project/Area Number 18509001
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Eating habits, studies on eating habits
Research InstitutionUniversity 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
Keywordscholesterol / 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 … 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

  • Research Products

    (28 results)

All 2008 2007

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (14 results) Book (2 results)

  • [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 promoters2008

    • Author(s)
      Sawa, T., Ohshima, H., et. al.
    • Journal Title

      Cancer Letters (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Geographic Distribution of Liver and Stomach Cancers in Thailand in Relation to Estimated Dietary Intake of Nitrate,Nitrite,and Nitrosodimethylamine2008

    • Author(s)
      Mitacek, E.J., Ohshima, H., et. al.
    • Journal Title

      Nutrition and Cancer 60

      Pages: 196-203

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Function alanalyses of neutrophil-like differentiated cell lines under a hyperglycemic condition2008

    • Author(s)
      Oya-lto, T., Masuda, S., et. al.
    • Journal Title

      Molecular Nutrition and Food Research 52(3)

      Pages: 360-369

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [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 promoters2008

    • Author(s)
      Sawa, T., Ohshima, et. al.
    • Journal Title

      Cancer Letters (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inflammation Induced Carcinogenesis and Chemoprevention2008

    • Author(s)
      H. Ohshima, S. Tomono, Y-L. Lai, N. Miyoshi
    • Journal Title

      Inflammation Induced Carcinogenesis and Chemoprevention (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Geographic Distribution of Liver and Stomach Cancers in Thailand in Relation to Estimated Dietary Intake of Nitrate, Nitrite, and Nitrosodimethylamine2008

    • Author(s)
      Mitacek, E. J., Ohshima, H., et. al.
    • Journal Title

      Nutrition and Cancer 60(2)

      Pages: 196-203

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Functional analyses of neutrophil-like differentiated cell lines under a hyperglycemic condition2008

    • Author(s)
      Oya-Ito T., Masuda, S., et. al.
    • Journal Title

      Molecular Nutrition and Food Research 52(3)

      Pages: 360-369

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerate sarcoma development in Trp53+/-mice2007

    • Author(s)
      Tazawa, H., Ohshima, H., et. al.
    • Journal Title

      Carcinogenesis 28(1)

      Pages: 191-198

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Evaluation of mutagenic activities of leachates inlandfill sites by micronucleus test and comet assay using goldfish2007

    • Author(s)
      Deguchi, Y., Masuda, S., et. al.
    • Journal Title

      Mutat.Res 627(2)

      Pages: 178-185

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] リーブ葉エキス含有食品の抗酸化性、血糖値低減およびAGEs生成抑制効果2007

    • Author(s)
      佐々木 裕、増田 修一, 他
    • Journal Title

      健康・栄養食品研究 10

      Pages: 12-20

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerate sarcoma development in Trp53+/- mice2007

    • Author(s)
      Tazawa, H., Ohshima, H., et. al.
    • Journal Title

      Carcinogenesis 28(1)

      Pages: 191-8

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Evaluation of mutagenic activities of leachates in landfill sites by micronucleus test and comet assay using goldfish2007

    • Author(s)
      Deguchi, Y., Masuda, S., et. al.
    • Journal Title

      Mutat. Res 627(2)

      Pages: 178-185

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Year and Date
      20080216-19
    • Description
      「研究成果報告書概要(和文)」より
  • [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
    • Year and Date
      20080016-19
    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Year and Date
      20071212-15
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Nitrative DNA damage in inflammation and carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H., Kawanishi, S
    • Organizer
      ICoFF2007-International Conference on Food Factors for Health Promotion
    • Place of Presentation
      Kyoto,Japan
    • Year and Date
      20071128-1201
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Nitrative DNA damage in inflammation and carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H., Kawanishi, S
    • Organizer
      Invited speaker at the ICoF F2007
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20071128-1201
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Molecular mechanism of selective cytotoxicity by chemopreventive isothiocyanates2007

    • Author(s)
      Miyoshi, N., Nakamura, Y., Ohshima, H
    • Organizer
      International Conference on Food Factors for Health Promotion
    • Place of Presentation
      Kyoto
    • Year and Date
      20071127-1201
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] The role of nitrative DNA damage in inflammation-associated2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H., Kawanishi, S
    • Organizer
      The 1st International Conference on Nitric Oxide(NO)and Cancer
    • Place of Presentation
      Paris,France
    • Year and Date
      20071126-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The role of nitrative DNA damage in inflammation-associated carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H., Kawanishi, S
    • Organizer
      Invited speaker at the 1st International Conference on Nitric Oxide (NO) and Cancer
    • Place of Presentation
      Paris, France
    • Year and Date
      20071126-28
    • Description
      「研究成果報告書概要(欧文)」より
  • [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
    • Year and Date
      20071014-19
    • Description
      「研究成果報告書概要(和文)」より
  • [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
    • Year and Date
      20071014-19
    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Presentation] Molecular mechanism of selective cytotoxicity by chemopreventive isothiocyanates2007

    • Author(s)
      Miyoshi, N., Nakamura, Y., Ohshuna, H
    • Organizer
      International Conference on Food Factors for Health Promotion
    • Place of Presentation
      Kyoto,Japan
    • Year and Date
      2007-10-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] DNA and protein damage induced by inflammatory oxidnts:role in carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H
    • Organizer
      The 2007 International Symposium on Advanced Bioscience
    • Place of Presentation
      Cheongju,Korea
    • Year and Date
      2007-06-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] DNA and protein damage induced by inflammatory oxidnts: role in carcinogenesis2007

    • Author(s)
      Ohshima, H., Sawa, T., Tazawa, H
    • Organizer
      Invited speaker at the 2007 International Symposium on Advanced Bioscience
    • Place of Presentation
      Cheongju, Korea
    • Year and Date
      2007-06-15
    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Book] がん予防『酸化ストレスの医学』2008

    • Author(s)
      大島 寛史, 三好 規之
    • Publisher
      診断と治療社(印刷中)
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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