Arsenic trioxide suppresses liver X receptor beta and enhances cholesteryl ester transfer protein expression without affecting the liver X receptor alpha in HepG2 cells

作者：Cheng Tain Junn; Lin Shu Wen; Chen Chih Wei; Guo How Ran^*; Wang Ying Jang^*

来源：Chemico-Biological Interactions, 2016, 258: 288-296.

DOI：10.1016/j.cbi.2016.09.009

• Arsenic
• Atherosclerosis
• Liver X receptor
• Cholesteryl ester transfer protein
• Sterol regulatory element-binding protein
• Reverse cholesterol transport

Chronic arsenic exposure is associated with cerebrovascular disease and the formation of atherosclerotic lesions. Our previous study demonstrated that arsenic trioxide (ATO) exposure was associated with atherosclerotic lesion formation through alterations in lipid metabolism in the reverse cholesterol transport process. In mouse livers, the expression of the liver X receptor beta (LXR-beta) and the cholesteryl ester transfer protein (CETP) was suppressed without any changes to the lipid profile. The aim of this study was to elucidate whether ATO contributes to atherosclerotic lesions by suppressing LXR-beta and CETP levels in hepatocytes. HepG2 cells, human hepatocytes, were exposed to different ATO concentrations in vitro. Cell viability was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. The liver X receptor alpha (LXR-alpha), LXR-beta, sterol regulatory element-binding protein-1c (SREBP-1c) and CETP protein levels were measured by Western blotting, and their mRNA levels were measured by real-time PCR. Cholesterol efflux was analyzed by flow cytometry.
The results showed ATO inhibited LXR-beta mRNA and protein levels with a subsequent decrease in SREBP-1c protein levels and reduced cholesterol efflux from HepG2 cells into the extracellular space without influencing LXR-alpha mRNA and protein levels. CETP protein levels of HepG2 cells were significantly elevated under arsenic exposure. Transfection of LXR-beta shRNA did not change CETP protein levels, implying that there is no cross-talk between LXR-beta and CETP. In conclusion, arsenic not only inhibits LXR-beta and SREBP-1c mRNA and protein levels but also independently increases CETP protein levels in HepG2 cells.

• 出版日期2016-10-25
• 单位中国医科大学