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Analysis of the hydroperoxides component in oxidi zed LDL

Research Project

Project/Area Number 11557174
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Physical pharmacy
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

KUROSAWA Takao  Fac. Pharm., Sci. Health Sci. Univ., Prof., 薬学部, 教授 (50103198)

Co-Investigator(Kenkyū-buntansha) YOSHIMURA Teruki  Fac. Pharm. Sci., Ass. Prof., 薬学部, 助教授 (60220737)
AOKI Takashi  Sch. Medicine, Hokkaidoi Univ., Ass. Prof., 薬学部, 助教授 (90184035)
CHIBA Hitoshi  Fac. Pharm., Sci. Health Sic. Univ., Prof., 医学部, 講師 (70197622)
KOHNO Hiroaki  Kyowa Medex Co., Researcher, 主任研究員
MURAI Tuyoshi  Fac. Pharm. Sci., Ass. Instructor, 薬学部, 助手 (50260823)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2000: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1999: ¥6,200,000 (Direct Cost: ¥6,200,000)
Keywordsoxidized LDL / cholesterol ester / triglyceride / hydroperoxide / CETP / CD36 / HPLC / 脂肪酸過酸化物
Research Abstract

Purpose
It is known that oxidized lipoprotein in the endodermis is important for the generation of the arteriosclerosis. Recently, the existence of the oxidized lipoprotein in blood plasma has been confirmed. However, chemical property and metabolic regulation mechanism of the oxidized lipoprotein in blood plasma arenot sufficiently known. The purpose of the present study carries out details qualitative analysis and quantitative analysis on lipid component (hydroperoxides) of the oxidized LDL in human serum in connection with several lipid associated disorders.
Results and Experimentals
In order to develop the analytical methods of hydroperoxides, the hydroperoxides of cholesterol esters (oleic, linoleic, linolenic acid esters) were first synthesized by the photo-sensitized oxidation. The structures of these hydroperoxides were confirmed by their spectral data after chromatographic separation into each diastereoisomeric isomer. Then hydroperoxides of triacyl glycerol are also synthesized by the above reactions, and triacy glycerols were synthesized by the photo-sensitized oxidation. Using these synthesized hydroperoxides, the analytical methods by high-performance liquid chromatography (fluorescent detection and chemiluminescent detection) were established and the present methods were peroxides in LDL fraction are higher than that of HDL fraction, showing that lipid hydroperoxides are existed in mostly LDL Fraction, i. e, oxidized LDL.
The analysis of the hydroperoxides in LDL and HDL fraction of the serum from Lipid disorders, such as cholesterol transfer proten (CETP) deficiency and CD36 deficiency, are now under investigation and the results should be apperred elsewhere. One of the aime of this research is the development of convenient assay of hydroperoxide in serum., such as EIA method. The research for development of the EIA method is now also under investigation to use cholesteryl linoleate hydroperoxides as hapten.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report

Research Products

(48 results)

All Other

All Publications (48 results)

  • [Publications] T.Yoshimura: "Enzyme immunoassay for conjugated 7a-hydroxy-3-oxo-4-cholenoic acid in human urine"J. Immunoassay. 22. 1-13 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Yanai: "Metabolic changes in human CD36 deficiency displayed by glucose loading"Thromb & Haemost. 86. 995-999 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Yamato: "Fetal bile acid metabolism : Analysis of urinary 3β-monohydroxy-Δ5-bile acids in preterm infants"Biology of the Neonate. 80. 19-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Yamato: "3β-Hydroxy-Δ5-steroid dehydrogenase deficiency-diagnosis and treatment"J. Paediatr. Child Health. 37. 516-519 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Kurosawa: "Conjugation reactions catalyzed by bifunctional proteins related to β-oxidayion in bile acid biosynthesis"Steroids. 66. 107-114 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Kurosawa: "Synthesis of coenzyme A esters of 3α, 7α, 12α-trihydroxy-and 3α, 7α-dihydroxy-24-oxo-5β-cholestan-26-oic acids for the study of β-oxidation in bile acid biosynthesis"Steroids. 66. 499-504 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Kobayashi: "3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase deficiency in a 23-year-old woman"Pediatr. Intern. 42. 685-688 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Yanai: "Phenotype-genotype correlation in CD36 deficiency types I and II"Thromb & Haemost. 83. 436-441 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Yanai: "Human CD36 deficiency is associated with elevation in low-density lipoprotein-cholesterol"Am. J. Med Genet. 93. 299-304 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.P.Hui: "Determination of regio-isomeric hydroperoxides of fatty acid cholesterol esters by photosensitized peroxidation using HPLC"Anal. Sci. 16. 1023-1028 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Kimura: "Abnormality low ratio of cholic acid to chenodeoxycholic acid due to a deficiency of 3-oxo-Δ4-steroid 5β-reductase"Pediatr. Int. 42. 594 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Bun-ya: "Metabolic Significance and Expression of Caenorhabditis elegans Type II 3-Oxoacyl-CoA Thiolase"Cell Biology and Biophisics. 32. 291-293 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Aoki: "A flexible single-step detection of blotted antigen using a fusion protein between protein A and green fluorescent protein"Biosci. Biotechnol. Biochem. 64. 1547-1551 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Kimura: "Profiles of Urinary Bile Acids in Infants and Children : Developmental Pattern of Excretion of Unsaturated Ketonic Bile acids and 7β-Hydroxylated Bile Acids"Pediatr. Res. 45. 603-609 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Watanabe: "Birirubin pigmentation of human teeth caused by hyperbilirubinemia"J. Oral Pathol. Med. 28. 128-130 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Taniguchi, D. Kobayashi, T. Koraiya, T. Murai, Kimura, T. Kurosawa, M. Tohma: "Enzyme iraraunoassay for conjugated 7αhydroxy - 3 - oxo - 4 -cholenoic acid in human urine."J. Imunoassay. 22 (1). 1-13 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Yanai, H. Chiba, H. Fujiwara, M. Moromoto, Y. Takahashi, S.P. Hui, H. Fuda, H. Akita, T. Kurosawa, K. Kobayashi, K. Matusno: "Metabolic changes in human. CD36 deficiency displayed by glucose loading"Thromb & Haemost.. 86. 995-999 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Yamato, A. Kimura, T. Kurosawa, H. Kato: "Fetal Bile Acid Metabolism : Analysis of Urinary 3β-Monohydroxy-Δ5-Bile Acids in Preterm Infants"Biology of the Neonate. 80. 19-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Yamato, A. Kimura, T. Murai, T. Yoshimura, T. Kurosawa, S. Terazawa, A. TaKao, K. Maeda, E. Nakashima, Y. Yaraashita, H. Kato: "3β- Hydroxyn-Δ5-steroid dehydroginase deficiency -diagnosis and treatment-"J. Peadiatr. Child Health. 37. 516-519 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Kurosawa, M. Fujiwara, H. Nakano, M. sato. T. Yoshimura. T. Murai: "Conjugation reactions catalyzed by bifunctional proteins related to β oxidayion in bile acid biosynthesis"Steroids. 66 (2). 107-114 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Kurosawa, M. Fujiwara, H. Nakano, M.. Sato, T. Yoshimura, T. Murai: "Synthesis of coenzyme A esters of 3α, 7α, 12α-trihydroxy-and 3α, 7α, dihydroxy-24-oxo-5β-cholestan-26-oic acids for the study of β-oxidation in bile acid biosynthesis"Steroids. 66 (6). 499-504 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Kobayashi. M. Koike, M. Sakiyama S. Okuda, M. Okuda, T. Tanaka, A. Unno, H. Nittono, H. Takei, T. Murai, T. Yoshimura, T. Kurosawa: "3β hydroxy-Δ5-C27-steroid dehydrogenase / isomerase deficiency in a 23-year old woman"Pesiatr. Intern.. 42. 685-688 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Yanai, H. Chiba, H. Fujiwara, M. Morimoto, K. Abe, S. Yoshida. Y. Takahashi, H. Fuda, S.P. Hui, Akita H, K. Kobayashi, K. Matsuno: "Phenotype-genotype correlation in CD36 deficiency types I and II"Thromb. Haemost. 83. 436-441 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Yanai, H. Chiba, M. Morimoto, K. Abe, H. Fujiwara, H. Fuda, S.P,Hui, Y. Takahashi. H. Akita. G. A. Jamieson, K. Kobaynshi, K. Matsuno: "Human CD36 deficiency is associated with elevation in low-density lipoprotein-cholestero1"Am. J. Med Genet.. 93. 299-304 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S.P. Hui, T. Yoshiraura, H. Chiba, T. Kurosawa: "Determination of regio-isomeric hydroperoxides of fatty acid cholesterol esters by photosensitized peroxidation using HPLC"Anal. Sci. 16. 1023-1028 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Kiraura, H. Nittono, H. Takei, T. Kurosawa: "Abnormality low ratio of cholic acid to chenodeoxycholic acid due to a deficiency of 3-oxo-Δ4-steroid 5β-reductase"Pedeatr. Int.. 42. 594 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Bun-ya, M. Maebuchi, S. H. Togo, T. Kurosawa, T. Hashimoto, T. Kamiryo: "Metabolic Significance and Expression of Caenorhabditis elegans Type II 3-Oxoacy-CoA Thiolase"Cell Biology and biophisics. 32. 291-293 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Aoki, M. Miyashita, H. Fujino, and H. Watabe: "A flexible single-step detection of blotted antigen using a fusion protein between protein and green fluorescent protein"Biosci. Biotechnol. Biochem.. 64. 1547-1551 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Kimura, R. Mahara, T. Inoue, Y. Nomura, T. Murai, T. Kurosawa, 1 Tohma, K. Noguchi, A.: "Profiles of Urinary Bile Acids in Infants and Children : Developmental Pattern of Excretion of Unsaturated Ketonic Bile acids and 7β-Hydrozylated Bile Acids"Pediatr. Res. 45. 603-609 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Watanabe, T. Shibata, T. Kurosawa, I. Morisaki, M. Kinehara, S. Igarashi, M. Arisue: "Birirubin pigmentation of human teeth caused by hyperbilirubinemia"J. Oral Pathol. Med.. 28. 128-130 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yoshimura: "Enzyme immunoassay for conjugated 7α-hydroxy-3-oxo-4-cholenoic acid in human urine"J.Immunoassay. 22. 1-13 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Yanai: "Metabolic changes in human CD36 deficiency displayed by glucose loading"Thromb &Haemost. 86. 995-999 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Yamato: "Fetal Bile Acid Metabolism : Analysis of Urinary 3β-Monohydroxy-Δ5-Bile Acids in Preterm Infants"Biology of the Neonate. 80. 19-25 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Yamato: "3β-Hydroxy-Δ5-steroid dehydrogenase deficiency -diagnosis and treatment -"J.Paediatr.Child Health. 37. 516-519 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kurosawa: "Conjugation reactions catalyzed by bifunctional proteins related to β-oxidayion in bile acid biosynthesis"Steroids. 66. 107-114 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kurosawa: "Synthesis of coenzyme A esters of 3α,7α,12α-trihydroxy-an 3α,7α-dihydroxy-24-oxo-5β-cholestan-26-oic acids for the study of β-oxidation in bile acid biosynthesis"Steroids. 66. 499-504 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kurosawa T: "Conjugation reactions catalyzed by bifunctional proteins related to β-oxidation in bile acid biosynthesis"Steroids. 66. 107-114 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurosawa T: "Synthesis of coenzyme A esters of 3α,7α,12α-trihydroxy-and 3α,7α-dihydroxy-24-oxo-5β-cholesta-26-oic acid for the study of b-oxidation in bile acid biosynthesis"Steroids. 66. 499-504 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hui S-P.: "Determination of Regioisomeric Hydroperoxides of Fatty Acid Cholesterol Eters Produced by Photosensitized Peroxidation using HPLC"Anal.Sci.. 16. 1023-1028 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yanai H.: "Human CD36 deficiency is associated with elevation in low -density lipoprotein metabolism and hemostasis"Am.J.Med.Genet.. 152. 299-304 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yanai H.: "Phenotype-genotype correlation in CD36 deficiency type I and II"Thromb.Haemost.. 84. 436-441 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Aoki T.: "A fexible single-step detection of blotted antigen using a fusion protein between protein A and green fluorescent protein"Biosci.Biotechnol.Biochem. 64. 1547-1551 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akihiro Kimura: "Protile urinary bile acids in infants and children :Developmenttal pattern of excretion of unsaturated ketonic bile acids and 7b-hydroxylated bile acids"Pediaric Research. 45. 603-609 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 千葉仁志: "CETP欠損症研究の最近の進歩"臨床検査. 44. 213-215 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasuda S.: "b2-Glycoprotein I deficiency: prevalence,genetic background effect on plasma lipoprotein metabolism"Atherosclerosis. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Yanai H.: "Type I CD36 deficiency in human not associated with insulin resistance syndrome"Am.J.Med.Genet.. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Matubara M.: "Decreased logevity in Japanese associated with low-molecular-weight apolipoprotein(a) phenotypes"Annals Clin.Biochem.. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Hidekatsu Yanai: "Phenotype-genotype correlation in CD36 defficiency types I and II"Thromb.Haemost.. (印刷中).

    • Related Report
      1999 Annual Research Report

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Published: 1999-03-31   Modified: 2016-04-21  

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