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缩醛磷脂稳态失调会损害胆固醇生物合成。

Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis.

作者信息

Honsho Masanori, Abe Yuichi, Fujiki Yukio

机构信息

From the Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

From the Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

出版信息

J Biol Chem. 2015 Nov 27;290(48):28822-33. doi: 10.1074/jbc.M115.656983. Epub 2015 Oct 13.

Abstract

Plasmalogen biosynthesis is regulated by modulating fatty acyl-CoA reductase 1 stability in a manner dependent on cellular plasmalogen level. However, physiological significance of the regulation of plasmalogen biosynthesis remains unknown. Here we show that elevation of the cellular plasmalogen level reduces cholesterol biosynthesis without affecting the isoprenylation of proteins such as Rab and Pex19p. Analysis of intermediate metabolites in cholesterol biosynthesis suggests that the first oxidative step in cholesterol biosynthesis catalyzed by squalene monooxygenase (SQLE), an important regulator downstream HMG-CoA reductase in cholesterol synthesis, is reduced by degradation of SQLE upon elevation of cellular plasmalogen level. By contrast, the defect of plasmalogen synthesis causes elevation of SQLE expression, resulting in the reduction of 2,3-epoxysqualene required for cholesterol synthesis, hence implying a novel physiological consequence of the regulation of plasmalogen biosynthesis.

摘要

缩醛磷脂生物合成通过以依赖于细胞缩醛磷脂水平的方式调节脂肪酰辅酶A还原酶1的稳定性来调控。然而,缩醛磷脂生物合成调控的生理意义仍然未知。在此我们表明,细胞缩醛磷脂水平的升高会降低胆固醇生物合成,而不影响诸如Rab和Pex19p等蛋白质的异戊二烯化。对胆固醇生物合成中间代谢物的分析表明,细胞缩醛磷脂水平升高时,角鲨烯单加氧酶(SQLE)催化的胆固醇生物合成中的首个氧化步骤会因SQLE的降解而减少,SQLE是胆固醇合成中HMG - CoA还原酶下游的一个重要调节因子。相比之下,缩醛磷脂合成缺陷会导致SQLE表达升高,从而导致胆固醇合成所需的2,3 - 环氧角鲨烯减少,因此暗示了缩醛磷脂生物合成调控的一种新的生理后果。

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