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作者

Liu, M. Chen, Y. Zhang, L. Wang, Q. Ma, X. Li, X. Xiang, R. Zhu, Y. Qin, S. Yu, Y. Jiang, X.-C. Duan, Y. Han, J.

作者单位

College of Medicine, Nankai University, Tianjin, 300071, China Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China College of Life Sciences, Nankai University, 94 Weijin Rd., Tianjin, 300071, China f Taishan Medical University, Taian, 271000, China a State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China g State University of New York Downstate Medical Center, New York, NY 11203, United States Collaborative Innovation Center for Biotherapy, Nankai University, Tianjin, 300071, China

刊名

Journal of Biological Chemistry

年份

2015

卷号

Vol.290 No.23

页码

14418-14429

ISSN

0021-9258

摘要

Cholesteryl ester transfer protein transfers cholesteryl esters from high density lipoprotein to triglyceride-rich lipoproteins. CETP expression can be transcriptionally activated by liver X receptor . Etoposide and teniposide are DNA topoisomerase II inhibitors. Etoposide has been reported to inhibit atherosclerosis in rabbits with unfully elucidated mechanisms. In this study we determined if Topo II activity can influence cholesterol metabolism by regulating hepatic CETP expression. Inhibiti...更多

Cholesteryl ester transfer protein transfers cholesteryl esters from high density lipoprotein to triglyceride-rich lipoproteins. CETP expression can be transcriptionally activated by liver X receptor . Etoposide and teniposide are DNA topoisomerase II inhibitors. Etoposide has been reported to inhibit atherosclerosis in rabbits with unfully elucidated mechanisms. In this study we determined if Topo II activity can influence cholesterol metabolism by regulating hepatic CETP expression. Inhibition of Topo II by etoposide, teniposide, or Topo II siRNA increased CETP expression in human hepatic cell line, HepG2 cells, which was associated with increased CETP secretion and mRNA expression. Meanwhile, inhibition of LXR expression by LXR siRNA attenuated induction of CETP expression by etoposide and teniposide. Etoposide and teniposide induced LXRα expression and LXRα/β nuclear translocation while inhibiting expression of receptor interacting protein 140 , an LXR co-repressor. In vivo, administration of teniposide moderately reduced serum lipid profiles, induced CETP expression in the liver, and activated reverse cholesterol transport in CETP transgenic mice. Our study demonstrates a novel function of Topo II inhibitors in cholesterol metabolism by activating hepatic CETP expression and reverse cholesterol transport.收起

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