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

1999 Fiscal Year Final Research Report Summary

Cholesterol biosynthesic enzymes and inborn errors

Research Project

Project/Area Number 10044251
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionNiigata University

Principal Investigator

ONO Teruo  Niigata University, School of Medicine, Professor, 医学部, 教授 (00000927)

Co-Investigator(Kenkyū-buntansha) WATANABE Michitoshi  Niigata University, School of Medicine, Research Associate, 医学部, 助手 (40303127)
SAKAKIBARA Jun  Niigata University, School of Medicine, Research Associate, 医学部, 助手 (90242403)
Project Period (FY) 1998 – 1999
KeywordsSqualene Epoxidase (SE) / Langer-Giedion Syndrome / Transcriptional Regulation / Sterol Regulatroy Element (SRE) / SE Functional Domain / Intranuclear Receptor / Oxysterol
Research Abstract

The present study was undertaken to determine the chromosomal mapping of the human squalene epoxidase gene (SQLE). PCR evidence localizes human SQLE to chromosome 8 by hybrid panel as templete. Since the locus of the Langer-Giedion (LG) syndrome genes (8q24.1), a congenital abnormality, is close to the locus of human SQLE(8q24.1), SQLE is considered the candidate for the LG syndrome gene(s). The human SQLE consisted about 17 kb long and organized into 11 exons and 10 intorns ranging from 87 to 3.2 kb. We characterized a new SREBP-la and a typical NF-Y binding sites in the promoter of the human SE gene. Both sites are functional in the transcriptional levels of SQLE. Transcription of reporter genes of LXR responsive element (LXRE) and human SE promoter were studied with the effects of lipoprotein deficient serum (LPDS) and oxysterols in LXR α-transfected HeLa cells. Compared with LXR α transgene negative cells, LXRE was significantly induced by LPDS in positive cells and 25-hydroxycholesterol reinforced the induction. In contrast, SE was reciprocally suppressed under the same conditions. Transfection of LXR α mutant failed to support LXRE induction and SE suppression. Those induction and supporession were completely dependent on the LXRs overexpression and oxysterol ligands having specific structure. It is suggested that LXRs may involve in cholesterol homeostasis through the action of target gene product(s) of LXRs by suppressing SE, a key synthesizing enzyme of the endogenous oxysterol ligands for LXRs.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Nagai, M.: "Localization of the squalene cpoxidase gene(SQLE) to human chromosome 8q 24.1"Genomics. 44. 141-143 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Grieveson, L.A.: "A simplified squalene epoxidase assay based on an HPLC separation and time dependent UV/Visible determination of squalene"Anal. Biochem.. 252. 19-23 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 永井雅昭: "ヒトスクアレンエポキシダーゼ遺伝子の染色体マッピングとプロモーター解析"脂質生化学研究(JBCL). 39. 303-306 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小野輝夫: "スクアレン・エポキシダーゼの機能ドメインの解析-I"脂質生化学研究(JBCL). 40. 81-84 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanda, T.: "Regulation of the expression of human intestinal bile acid-binding protein in Caco-2 cells"Biochem. J.. 330. 261-265 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小野輝夫: "核内レセプターLXRのスクアレン・エポキシダーゼ遺伝子制御への関与"脂質生化学研究(JBCL). 41. 297-299 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Grober, J.: "Identification of a bile acid-responsive element in the human ileal bile acid binding protein gene. Involvement of the farnesoid X-receptor/9-cis-retinoic acid receptor heterodimer"J. Biol. Chem.. 274. 29649-29754 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe, I.: "Green tea polyphenols : Novel and potent inhibitors of squalene epoxidase"Biochem. Biophys. Res. Commun.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lee, H. K.: "Photoaffinity labeling and site-directed mutagenesis of rat squalene epoxidase"Arch. Biochem. Biophys.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagai, M.: "Localization of the squalene epoxidase gene (SQLE) to human chromosome 8q 24.1"Genomics. 44. 141-143 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Grieveson, L. A.: "A simplified squalene epoxidase assay bassed on an HPLC separation and time dependent UV/Visible determination of squalene"Anal. Biochem.. 252. 19-23 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanda, T.: "Regulation of the expression of human intestinal bile acid-binding protein in Caco-2 cells"Biochem. J.. 330. 261-265 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Grober, J.: "Identification of a bile acid-responsive element in the human ileal bile acid binding protein gene. Involvement of the fernesoid X-receptor/9-cis-retinoic acid receptor heterodimer"J. Biol. Chem.. 274. 29749-29754 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Abe, I.: "Green tea polyphenols : Novel and potent inhibitors of squalene epoxidase"Biochem. Biophys. Res. Commun.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lee, H. K.: "Photoaffinity labeling and site-directed mutagenesis of rat squalene epoxidase"Arch. Biochem. Biophys.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai, M.: "Hitosukuaren epokishidaze idenshi no Sensyokutai matsupingu to puromota kaiseki"SHISHITUSEIKAGAKUKENKYU (JBCL). 39. 303-306 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono, T.: "Sukuaren epokishidaze no kinodomein no Kaiseki-I"SHISHITUSEIKAGAKUKENKYU (JBCL). 40. 81-84 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono, T.: "Kakunaireseputa LXR no sukuaren epokishidaze idenshiseigyo he no kanyo"SHISHITUSEIKAGAKUKENKYU (JBCL). 41. 297-299 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2001-10-23  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi