Arsenic trioxide suppresses liver X receptor β and enhances cholesteryl ester transfer protein expression without affecting the liver X receptor α in HepG2 cells.
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 β (LXR-β) 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-β 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 α (LXR-α), LXR-β, 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-β 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-α mRNA and protein levels. CETP protein levels of HepG2 cells were significantly elevated under arsenic exposure. Transfection of LXR-β shRNA did not change CETP protein levels, implying that there is no cross-talk between LXR-β and CETP. In conclusion, arsenic not only inhibits LXR-β and SREBP-1c mRNA and protein levels but also independently increases CETP protein levels in HepG2 cells.
Department of Neurology and Occupational Medicine, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang Dist., Tainan 710, Taiwan; Department of Occupational Safety and Health/Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, 60 Sec. 1, Erren Road, Rende Dist., Tainan 71710, Taiwan.
Tain-Junn
TJ
Cheng
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
Shu-Wen
SW
Lin
Department of Occupational Safety and Health/Institute of Industrial Safety and Disaster Prevention, College of Sustainable Environment, Chia Nan University of Pharmacy and Science, 60 Sec. 1, Erren Road, Rende Dist., Tainan 71710, Taiwan; Division of Neurosurgery, Department of Surgery, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang Dist., Tainan 710, Taiwan.
Chih-Wei
CW
Chen
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan; Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan. Electronic address: hrguo@mail.ncku.edu.tw.
How-Ran
HR
Guo
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan; Department of Biomedical and Informatics, Asia University, 500 Lioufeng Road, Wufeng, Taichung, 41354, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, 500 Lioufeng Road, Wufeng, Taichung, 41354, Taiwan. Electronic address: yjwang@mail.ncku.edu.tw.
Ying-Jang
YJ
Wang
D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D001152:Arsenicals; D053480:Cholesterol Ester Transfer Proteins; D000071518:Liver X Receptors; D010087:Oxides; D051780:Sterol Regulatory Element Binding Protein 1; D002784:Cholesterol; D000077237:Arsenic Trioxide
Arsenic; Atherosclerosis; Cholesteryl ester transfer protein; Liver X receptor; Reverse cholesterol transport; Sterol regulatory element-binding protein