| Project/Area Number |
10044251
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Niigata University |
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Principal Investigator |
ONO Teruo Niigata University, School of Medicine, Professor, 医学部, 教授 (00000927)
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| 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)
EDWARDS P.A. UCLA大学, 医学部, 教授
SHECHTER I USU大学, 医学部, 教授
SCHROEPFER G Rice大学, 化学部, 教授
藤井 博 新潟大学, 医学部, 助教授 (90165340)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | Squalene Epoxidase (SE) / Langer-Giedion Syndrome / Transcriptional Regulation / Sterol Regulatroy Element (SRE) / SE Functional Domain / Intranuclear Receptor / Oxysterol / スクアレンエポ キシダーゼ(SE) |
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| 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.
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