核内リセプターLXRによるコレステロール合成系遺伝子の制御

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書誌事項

タイトル別名
  • Regulation of the Gene Involved in Cholesterol Biosynthesis by Nuclear Receptor LXR
公開日
1999-10
資源種別
departmental bulletin paper
公開者
新潟医学会

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説明

We had shown that squalene epoxidase (SE) gene, which is one of the enzymes in cholesterol biosynthesis, is regulated by oxysterol, and SE is able to synthesize one of the oxysterol, epoxycholesterol. Recently, it was reported that the ligands of nuclear receptor LXRs and Ad 4 BP/SF-1 are oxysterols. We have studied whether LXRs are involved in the signal transduction pathway from oxysterol to transcriptional factors regulating cholesterol metabolism related genes or not. Our data show over expression of LXR in HeLa cells cause to induction of LXRE (LXR-response element) drived gene, while suppression of SE promoter drived gene. Most efficient inducer to LXRE is proved to be epoxycholesterol, and in order according to induction ability, 22R-hydroxycholesterol, 20α-hydroxycholesterol, 25-hydroxycholesterol and 22S-hydroxycholesterol. Induction ability to LXRE of oxysterols correlates suppression ability to SE promoter. The quantity of epoxycholesterol, putative physiological LXR ligand, must be regulated by the ratio of activities of SE and following enzyme lanosterol synthase. Tissue specificities of the two enzymes show extremely different pattern. It is possible that the epoxycholesterol works as hormone in various tissue.

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