The orphan nuclear receptor Nur77 regulates hepatic cholesterol metabolism through the suppression of LDLR and HMGCR expression

被引:15
作者
Zhang, Peng [1 ]
Hu, Yanwei [1 ]
Yang, Junyao [1 ]
Zheng, Lei [1 ]
Wang, Qian [1 ]
机构
[1] So Med Univ, Nanfang Hosp, Dept Lab Med, Guangzhou 510515, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Nur77; HepG2; cells; cholesterol metabolism; low-density lipoprotein receptor; HMGCoA reductase; CANCER CELLS; APOPTOSIS; GENES; ALPHA; NURR1; TR3;
D O I
10.3892/mmr.2012.850
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Disorders in cholesterol metabolism are critical in development of atherosclerosis and are related to acute myocardial infarction (AMI). The liver is one of the most important organs that balances cholesterol metabolism. In order to investigate whether Nur77 is capable of regulating cholesterol metabolism in HepG2 cells and to demonstrate the underlying mechanism, the downregulation and upregulation of Nur77 expression in HepG2 cells was achieved by the transfection of siRNA specific to Nur77 and the transfection of the recombinant plasmid, pcDNA3.1-Nur77, respectively. Following the downregulation and upregulation of Nur77 expression, changes in the total cholesterol (TCHO) levels in HepG2 cells were observed based on lipid overloading. Thereafter, changes in a series of key gene expressions related to hepatic cholesterol metabolism were measured at the mRNA and protein levels by RT-PCR and western blot analysis, respectively. The TCHO levels in the HepG2 cells were found to increase following the downregulation of Nur77 expression and to decrease following the upregulation of Nur77 expression; these results were confirmed by oil red O staining of the cells. As for the hepatic cholesterol metabolism genes, low-density lipoprotein receptor (LDLR) and HMGCoA reductase (HMGCR) levels increased following the downregulation of Nur77 expression and decreased following the upregulation of Nur77 expression. However, liver X receptor alpha (LXR alpha) expression did not change markedly along with that of Nur77. According to these findings, we conclude that Nur77 is capable of reducing hepatic cholesterol based on lipid overloading, and this may be due to the decrease in LDLR and HMGCR levels.
引用
收藏
页码:1541 / 1547
页数:7
相关论文
共 24 条
[1]   Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses [J].
Bonta, Peter I. ;
van Tiel, Claudia M. ;
Vos, Mariska ;
Pols, Thijs W. H. ;
van Thienen, Johannes V. ;
Ferreira, Valerie ;
Arkenbout, E. Karin ;
Seppen, Jurgen ;
Spek, C. Arnold ;
van der Poll, Tom ;
Pannekoek, Hans ;
de Vries, Carlie J. M. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (10) :2288-2294
[2]   Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle [J].
Chao, Lily C. ;
Zhang, Zidong ;
Pei, Liming ;
Saito, Tsugumichi ;
Tontonoz, Peter ;
Pilch, Paul F. .
MOLECULAR ENDOCRINOLOGY, 2007, 21 (09) :2152-2163
[3]   Insulin Resistance and Altered Systemic Glucose Metabolism in Mice Lacking Nur77 [J].
Chao, Lily C. ;
Wroblewski, Kevin ;
Zhang, Zidong ;
Pei, Liming ;
Vergnes, Laurent ;
Ilkayeva, Olga R. ;
Ding, Shi Ying ;
Reue, Karen ;
Watt, Matthew J. ;
Newgard, Christopher B. ;
Pilch, Paul F. ;
Hevener, Andrea L. ;
Tontonoz, Peter .
DIABETES, 2009, 58 (12) :2788-2796
[4]   Orphan nuclear receptors:: From gene to function [J].
Giguère, V .
ENDOCRINE REVIEWS, 1999, 20 (05) :689-725
[5]   A human hepatocellular in vitro model to investigate steatosis [J].
Gomez-Lechon, Maria Jose ;
Donato, Maria Teresa ;
Martinez-Romero, Alicia ;
Jimenez, Nuria ;
Castell, Jose Vicente ;
O'Connor, Jose-Enrique .
CHEMICO-BIOLOGICAL INTERACTIONS, 2007, 165 (02) :106-116
[6]   The mammalian low-density lipoprotein receptor family [J].
Hussain, MM ;
Strickland, DK ;
Bakillah, A .
ANNUAL REVIEW OF NUTRITION, 1999, 19 :141-172
[7]   Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3 [J].
Li, H ;
Kolluri, SK ;
Gu, J ;
Dawson, MI ;
Cao, XH ;
Hobbs, PD ;
Lin, BZ ;
Chen, GQ ;
Lu, LS ;
Lin, F ;
Xie, ZH ;
Fontana, JA ;
Reed, JC ;
Zhang, XK .
SCIENCE, 2000, 289 (5482) :1159-1164
[8]  
Maxwell Megan A, 2006, Nucl Recept Signal, V4, pe002
[9]  
Meinke G, 1999, NAT STRUCT BIOL, V6, P471
[10]   NERVE GROWTH-FACTOR INDUCES A GENE HOMOLOGOUS TO THE GLUCOCORTICOID RECEPTOR GENE [J].
MILBRANDT, J .
NEURON, 1988, 1 (03) :183-188