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Sulfated oxysterol, 25HC3S, is a potent regulator of lipid metabolism in human hepatocytes.

Abstract：

:Recently, a novel oxysterol, 5-cholesten-3beta, 25-diol 3-sulfate (25HC3S) was identified in primary rat hepatocytes following overexpression of the cholesterol transport protein, StarD1. This oxysterol was also detected in human liver nuclei. In the present study, 25HC3S was chemically synthesized. Addition of 25HC3S (6 microM) to human hepatocytes markedly inhibited cholesterol biosynthesis. Quantitative RT-PCR and Western blot analysis showed that 25HC3S markedly decreased HMG-CoA reductase mRNA and protein levels. Coincidently, 25HC3S inhibited the activation of sterol regulatory element binding proteins (SREBPs), suggesting that inhibition of cholesterol biosynthesis occurred via blocking SREBP-1 activation, and subsequently by inhibiting the expression of HMG CoA reductase. 25HC3S also decreased SREBP-1 mRNA levels and inhibited the expression of target genes encoding acetyl CoA carboxylase-1 (ACC-1) and fatty acid synthase (FAS). In contrast, 25-hydroxycholesterol increased SREBP1 and FAS mRNA levels in primary human hepatocytes. The results imply that 25HC3S is a potent regulator of SREBP mediated lipid metabolism.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Ren S,Li X,Rodriguez-Agudo D,Gil G,Hylemon P,Pandak WM

doi

10.1016/j.bbrc.2007.06.143

subject

Has Abstract

pub_date

2007-09-07 00:00:00

pages

802-8

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)01393-9

journal_volume

360

pub_type

杂志文章

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