Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells

被引：64

作者：

Bai, Qianming ^{[1
,2
]}

Xu, Leyuan ^{[1
]}

Kakiyama, Genta ^{[1
]}

Runge-Morris, Melissa Ann ^{[3
]}

Hylemon, Phillip B. ^{[4
]}

Yin, Lianhua ^{[2
]}

Pandak, William M. ^{[1
]}

Ren, Shunlin ^{[1
]}

机构：

[1] Virginia Commonwealth Univ, McGuire Vet Affairs Med Ctr, Dept Med, Richmond, VA 23249 USA

[2] Fudan Univ, Dept Physiol & Pathophysiol, Shanghai Med Coll, Shanghai 200032, Peoples R China

[3] Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48207 USA

[4] Virginia Commonwealth Univ, McGuire Vet Affairs Med Ctr, Dept Microbiol Immunol, Richmond, VA 23249 USA

来源：

ATHEROSCLEROSIS | 2011年 / 214卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Cytosolic sulfotransferase (SULT2B1b); 25-Hydroxycholesterol (25HC); 25-Hydroxycholesterol-3-sulfate (25HC3S); Oxysterol sulfation; Lipid metabolism; BILE-ACID SYNTHESIS; ORPHAN NUCLEAR RECEPTORS; PRIMARY RAT HEPATOCYTES; IN-VIVO; CHOLESTEROL; METABOLISM; OXYSTEROL; EXPRESSION; LIVER; TRANSCRIPTION;

D O I：

10.1016/j.atherosclerosis.2010.11.021

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objective: 25-Hydroxycholesterol (25HC) and its sulfated metabolite, 25-hydroxycholesterol-3-sulfate (25HC3S), regulate certain aspects of lipid metabolism in opposite ways. Hence, the enzyme for the biosynthesis of 25HC3S, oxysterol sulfotransferase (SULT2B1b), may play a crucial role in regulating lipid metabolism. We evaluate the effect of 25HC sulfation on lipid metabolism by overexpressing the gene encoding SULT2B1b in human aortic endothelial cells (HAECs) in culture. Methods and results: The human SULT2B1b gene was successfully overexpressed in HAECs following infection using a recombinant adenovirus. HPLC analysis demonstrated that more than 50% of H-3-25HC was sulfated in 24 h following overexpression of the SULT2B1b gene. In the presence of 25HC, SULT2B1b overexpression significantly decreased mRNA and protein levels of LXR, ABCA1, SREBP-1c, ACC-1, and FAS, which are key regulators of lipid biosynthesis and transport; and subsequently reduced cellular lipid levels. Overexpression of the gene encoding SULT2B1b gave similar results as adding exogenous 25HC3S. However, in the absence of 25HC or in the presence of T0901317, synthetic liver oxysterol receptor (LXR) agonist, SULT2B1b overexpression had no effect on the regulation of key genes involved in lipid metabolism. Conclusions: Our data indicate that sulfation of 25HC by SULT2B1b plays an important role in the maintenance of intracellular lipid homeostasis via the LXR/SREBP-1c signaling pathway in HAECs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：350 / 356

页数：7

共 31 条

[1]

Nuclear receptors and lipid physiology: Opening the X-files [J].

Chawla, A ;

Repa, JJ ;

Evans, RM ;

Mangelsdorf, DJ .

SCIENCE, 2001, 294 (5548) :1866-1870

[2]

Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver [J].

Chen, GX ;

Liang, GS ;

Ou, JF ;

Goldstein, JL ;

Brown, MS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (31) :11245-11250

[3]

Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice [J].

Chen, Wenling ;

Chen, Guoxen ;

Head, Daphne L. ;

Mangelsdorf, David J. ;

Russell, David W. .

CELL METABOLISM, 2007, 5 (01) :73-79

[4]

24-Hydroxycholesterol Sulfation by Human Cytosolic Sulfotransferases: Formation of Monosulfates and Disulfates, Molecular Modeling, Sulfatase Sensitivity, and Inhibition of Liver X Receptor Activation [J].

Cook, Ian T. ;

Duniec-Dmuchowski, Zofia ;

Kocarek, Thomas A. ;

Runge-Morris, Melissa ;

Falany, Charles N. .

DRUG METABOLISM AND DISPOSITION, 2009, 37 (10) :2069-2078

[5]

Not acute but chronic hypertriglyceridemia is associated with impaired endothelium-dependent vasodilation - Reversal after lipid-lowering therapy by atorvastatin [J].

de Man, FH ;

Weverling-Rijnsburger, AWE ;

van der Laarse, A ;

Smelt, AHM ;

Jukema, JW ;

Blauw, GJ .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (03) :744-750

[6]

FOLCH J, 1957, J BIOL CHEM, V226, P497

[7]

Oxysterols are substrates for cholesterol sulfotransferase [J].

Fuda, Hirotoshi ;

Javitt, Normal B. ;

Mitamura, Kuniko ;

Ikegawa, Shigeo ;

Strott, Charles A. .

JOURNAL OF LIPID RESEARCH, 2007, 48 (06) :1343-1352

[8]

Reciprocal relationships between abnormal metabolic parameters and endothelial dysfunction [J].

Han, Seung Hwan ;

Quon, Michael J. ;

Koh, Kwang Kon .

CURRENT OPINION IN LIPIDOLOGY, 2007, 18 (01) :58-65

[9]

SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver [J].

Horton, JD ;

Goldstein, JL ;

Brown, MS .

JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (09) :1125-1131

[10]

Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes [J].

Horton, JD ;

Shah, NA ;

Warrington, JA ;

Anderson, NN ;

Park, SW ;

Brown, MS ;

Goldstein, JL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (21) :12027-12032

← 1 2 3 4 →