A possible mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons

• Published in: Biochemical and biophysical research communications Vol. 335; no. 1; pp. 220 - 226
• Main Authors: Iwano, Shunsuke, Nukaya, Manabu, Saito, Tetsuya, Asanuma, Fumie, Kamataki, Tetsuya
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.09.2005
• Subjects: ABCA1; Arteriosclerosis - chemically induced; Arteriosclerosis - genetics; Arteriosclerosis - metabolism; Benz(a)Anthracenes - pharmacology; Benz(a)Anthracenes - toxicity; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - metabolism; Cell Line, Tumor; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; FAS; Gene Expression Regulation - drug effects; Humans; Liver X Receptors; Luciferase assay; LXR; Models, Biological; Orphan Nuclear Receptors; PAHs; Polycyclic Aromatic Hydrocarbons - pharmacology; Polycyclic Aromatic Hydrocarbons - toxicity; Quantitative RT-PCR; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; Receptors, Cytoplasmic and Nuclear - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; SCD; SREBP-1c; Sterol Regulatory Element Binding Protein 1; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - drug effects; Transcription, Genetic - genetics; ABCA1; Quantitative RT-PCR; SCD; LXR; PAHs; FAS; Luciferase assay; SREBP-1c
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.07.062

Polycyclic aromatic hydrocarbons (PAHs), aryl hydrocarbon receptor (AHR) ligands, induce atherogenesis. Liver X receptor (LXR) α is known to be involved in the control of cholesterol homeostasis. Thus, the purpose of this study was to investigate the effects of 3-methlycholanthrene (MC), one of the PAHs, on LXRα-mediated signal transductions. We found that expression of mRNAs for ATP binding cassette A1, sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase, and stearoyl-CoA desaturase was suppressed by treatment of HepG2 cells with MC. A luciferase reporter assay revealed that LXRα- and SREBP-1c-mediated transactivations were inhibited by MC via AHR. Based on these lines of evidence, we propose that down-regulation of the LXRα-regulated genes by PAHs is one of the causes responsible for atherosclerosis induced by PAHs.