• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Investigation of a novel pathogenesis of thrombosis-regulation of protein S by sex hormones and its abnormality-

Research Project

Project/Area Number 16590910
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKyushu University

Principal Investigator

OHNAKA Keizo  Kyushu University, Graduate Scholl of Medical Sciences, Assistant Professor (30325518)

Co-Investigator(Kenkyū-buntansha) HAMASAKI Naotaka  KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor (00091265)
TAKAYANAGI Ryoichi  KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor (30154917)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsPROTEINS / THROMBOSIS / HORMONE REPLACEMENT THERAPY / ESTROGEN
Research Abstract

1. Investigation of regulatory mechanism of the protein S gene by sex hormone
The effect of various sex hormones on promoter activity of the human protein S gene was examined using plasmid constructs carrying the promoter region of the human protein S gene and luciferase gene in cultured human hepatoma cells. Estrogen suppressed the transcriptional activity of the human protein S gene. Twelve base pairs region in the promoter of the human protein S gene was involved in the inhibitory effect of estrogen on protein S gene transcription.
2. Development of protein S measurement and investigation of regulatory mechanism of protein S in mice
An assay system of mouse protein S was developed by modification of human protein S measurement method. Using this system, we investigated the effects of sex hormones on the protein S level in mice. The plasma level of protein S decreased by treatment of estrogen and human gonadotropin as well as by pregnancy.
3. Association study of protein S polymorphism with the plasma protein S level in Japanese women
We examined the plasma free protein S level in a general Japanese population, and investigated the association of single nucleotide polymorphisms (SNPs) of the protein S gene (PROS1) with the plasma protein S level. Three of 379 Japanese women aged 50-75 years showed reduced plasma free protein S. One of these three had a heterozygous missense mutation (R275C) in the PROS1 gene. Furthermore, 11 individuals were heterozygous carriers with a K155E mutation. We conclude that the estimated prevalence of inherited protein S deficiency in Japanese women is at least 3.2% (12/379). Association analyses showed that a promoter SNP in the PROS1 gene was significantly associated with the free protein S level.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (29 results)

All 2007 2006 2005 2004

All Journal Article (29 results)

  • [Journal Article] Nuclear compartmentalization of N-CoR and its interactions with steroid receptors2007

    • Author(s)
      Shimoda S, et. al.
    • Journal Title

      Endocr J 54(3)

      Pages: 413-424

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification and synergism of cis-acting elements essential for basal promoter activity of the human type langiotensin II receptor gene in PLC-PRF-5 cells2007

    • Author(s)
      Shimoda S, Ohnaka K. Sakai Y, Nawata H, Takayanagi R
    • Journal Title

      Endocr J 54(3)

      Pages: 413-424

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nuclear compartmentalization of N-CoR and its interactions with steroid receptors2006

    • Author(s)
      Wu Y, et. al.
    • Journal Title

      Mol Cell Biol 26(17)

      Pages: 6633-6655

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Testicular zinc finger protein recruits histone deacetylase 2 and suppresses the transactivation function and intranuclear foci formation of agonist-bound androgen receptor competitively with TIF22006

    • Author(s)
      Tao R-H, et. al.
    • Journal Title

      Mol Cell Endocrinol 247(1-2)

      Pages: 150-165

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nuclear compartmentalization of N-CoR and its interactions with steroid receptors2006

    • Author(s)
      Wu Y, Kawate H, Ohnaka K. Nawata H, Takayanagi R
    • Journal Title

      Mol Cell Biol 26(17)

      Pages: 6633-6655

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Testicular zinc finger protein recruits histone deacetylase 2 and suppresses the transactivation function and intranuclear foci formation of agonist-bound androgen receptor competitively with TLF22006

    • Author(s)
      Tao R-H, Kawate H, Wu Y, Ohnaka K, Ishizuka M, Inoue A, Hagiwara H, Takayanagi R
    • Journal Title

      Mol Cell Endocrinol 247(1-2)

      Pages: 150-165

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nuclear compartmentalization of N-CoR and its interactions with steroid receptors2006

    • Author(s)
      Wu Y.at al.
    • Journal Title

      Mol Cell Biol 26(17)

      Pages: 6633-6655

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Wntシグナル系とステロイド骨粗鬆症2006

    • Author(s)
      大中 佳三
    • Journal Title

      CLINICAL CALCIUM 16(11)

      Pages: 1812-1816

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Testicular zinc finger protein recruits histone deacetylase 2 and suppresses the transactivation function and intranuclear foci formation of agonist-bound androgen receptor competitively with TIF22006

    • Author(s)
      Tao R-H, at al.
    • Journal Title

      Mol Cell Endocrinol 247(1-2)

      Pages: 150-165

    • Related Report
      2006 Annual Research Report
  • [Journal Article] グルココルチコイドとカルシウム骨代謝2006

    • Author(s)
      大中 佳三, 高柳 涼一
    • Journal Title

      内分泌・糖尿病科 23(suppl.3)

      Pages: 80-85

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ルグココルチコイドの骨代謝作用機構 : 分化促進と骨形成抑制2006

    • Author(s)
      大中 佳三, 高柳 涼一
    • Journal Title

      腎と骨代謝 19(2)

      Pages: 107-114

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Impaired nuclear translocation,nuclear matrix targeting,and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-billding domain derived from androgen insensitivity syndrome patients2005

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

      J CIin Endocrinol Metab 90(11)

      Pages: 6162-6169

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts2005

    • Author(s)
      Ohnaka K, et. al.
    • Journal Title

      Biochem Biophys Res Commun 329(1)

      Pages: 177-181

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Impaired nuclear translocation, nuclear matrix targeting, and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androgen insensitivity syndrome patients2005

    • Author(s)
      Kawate H, Wu Y, Ohnaka K, Tao R-H, Nakamura K, Okabe T, Yanase T, Nawata H, Takayanagi R
    • Journal Title

      J Clin Endocrinol Metab 90(11)

      Pages: 6162-6169

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts2005

    • Author(s)
      Ohnaka K, Tanabe M, Kawate H, Nawata H, Takayanagi R
    • Journal Title

      Biochem Biophys Res Commun 329(1)

      Pages: 177-181

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts2005

    • Author(s)
      Keizo Ohnaka, et al.
    • Journal Title

      Biochem Biophys Res Commun 329(1)

      Pages: 177-181

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Impaired nuclear translocation, nuclear matrix targeting, and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androgen insensitivity syndrome patients2005

    • Author(s)
      Hisaya Kawate, et al.
    • Journal Title

      J Clin Endocrinol Metab 90(11)

      Pages: 6162-6169

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole2005

    • Author(s)
      Cheng W, et al.
    • Journal Title

      Toxicol Appl Pharmacol 207(3)

      Pages: 187-194

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ステロイド性骨粗鬆症発症の新機構-グリココルチコイドによるWntシグナルの抑制-2005

    • Author(s)
      大中 佳三, 高柳 涼一
    • Journal Title

      Osteoporosis Japan 13(2)

      Pages: 299-301

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 加齢による血管内皮機能の変化2005

    • Author(s)
      大中 佳三, 高柳 涼一
    • Journal Title

      日本臨床 63(6)

      Pages: 989-993

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ステロイド性骨粗鬆症の発症メカニズム2005

    • Author(s)
      大中 佳三, 高柳 涼一
    • Journal Title

      総合臨床 54(11)

      Pages: 2810-2816

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts:novel mechanism of glucocorticoid 「-induced osteoporosis2004

    • Author(s)
      Ohnaka K, et. al.
    • Journal Title

      Biochem Biophys Res Commun 318(1)

      Pages: 259-264

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts : novel mechanism of glucocorticoid-induced osteoporosis2004

    • Author(s)
      Ohnaka K, Taniguchi H, Kawate H, Nawata H, Takayanagi R
    • Journal Title

      Biochem Biophys Res Commun 318(1)

      Pages: 259-264

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts : novel mechanism of glucocorticoid-induced osteoporosis2004

    • Author(s)
      Keizo Ohnaka
    • Journal Title

      Biochem Biophys Res Commun 318(1)

      Pages: 259-264

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of a new colorimetric method for protein S activity measurement2004

    • Author(s)
      Tomohide Tsuda
    • Journal Title

      Clin Chem Lab Med 42(3)

      Pages: 350-352

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Constitutive nitric oxide production in bovine aortic and brain microvascular endothelial cells : a comparative study2004

    • Author(s)
      Chiwaka Kimura
    • Journal Title

      J Physiol 554(Pt 3)

      Pages: 721-730

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ステロイド性骨粗鬆症発症の分子機構2004

    • Author(s)
      大中 佳三
    • Journal Title

      Osteoporosis Jpn 12(2)

      Pages: 317-320

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Rho-kinase阻害剤2004

    • Author(s)
      大中 佳三
    • Journal Title

      日本臨床 62(増刊号2)

      Pages: 571-574

    • Related Report
      2004 Annual Research Report
  • [Journal Article] スタチンとBMP2004

    • Author(s)
      大中 佳三
    • Journal Title

      CLINICAL CALCIUM 14(2)

      Pages: 286-288

    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi