当前位置： SCI文献检索 > JOURNAL OF LIPID RESEARCH期刊下所有文献 > On the regulatory role of side-chain hydroxylated oxysterols in the brain. Lessons from CYP27A1 transgenic and Cyp27a1(-/-) mice.

On the regulatory role of side-chain hydroxylated oxysterols in the brain. Lessons from CYP27A1 transgenic and Cyp27a1(-/-) mice.

Abstract：

:The two oxysterols, 27-hydroxycholesterol (27OH) and 24S-hydroxycholesterol (24OH), are both inhibitors of cholesterol synthesis and activators of the liver X receptor (LXR) in vitro. Their role as physiological regulators under in vivo conditions is controversial, however. In the present work, we utilized a previously described mouse model with overexpressed human sterol 27-hydroxylase (CYP27A1). The levels of 27OH were increased about 12-fold in the brain. The brain levels of HMG-CoA reductase mRNA and HMG-CoA synthase mRNA levels were increased. In accordance with increased cholesterol synthesis, most of the cholesterol precursors were also increased. The level of 24OH, the dominating oxysterol in the brain, was decreased by about 25%, most probably due to increased metabolism by CYP27A1. The LXR target genes were unaffected or slightly changed in a direction opposite to that expected for LXR activation. In the brain of Cyp27(-/-) mice, cholesterol synthesis was slightly increased, with increased levels of cholesterol precursors but normal mRNA levels of HMG-CoA reductase and HMG-CoA synthase. The mRNA levels corresponding to LXR target genes were not affected. The results are consistent with the possibility that both 24OH and 27OH are physiological suppressors of cholesterol synthesis in the brain. The results do not support the contention that 27OH is a general activator of LXR target genes in this organ.

journal_name

J Lipid Res

journal_title

Journal of lipid research

authors

Ali Z,Heverin M,Olin M,Acimovic J,Lövgren-Sandblom A,Shafaati M,Båvner A,Meiner V,Leitersdorf E,Björkhem I

doi

10.1194/jlr.M034124

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

1033-43

issue

4

eissn

0022-2275

issn

1539-7262

pii

jlr.M034124

journal_volume

54

pub_type

杂志文章

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