Abstract
Polycyclic aromatic hydrocarbons (PAHs), aryl hydrocarbon receptor (AHR) ligands, induce atherogenesis. Liver X receptor (LXR) alpha 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 LXRalpha-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 LXRalpha- and SREBP-1c-mediated transactivations were inhibited by MC via AHR. Based on these lines of evidence, we propose that down-regulation of the LXRalpha-regulated genes by PAHs is one of the causes responsible for atherosclerosis induced by PAHs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arteriosclerosis / chemically induced*
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Arteriosclerosis / genetics
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Arteriosclerosis / metabolism
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Benz(a)Anthracenes / pharmacology
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Benz(a)Anthracenes / toxicity
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CCAAT-Enhancer-Binding Proteins / genetics
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CCAAT-Enhancer-Binding Proteins / metabolism
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Cell Line, Tumor
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation / drug effects
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Humans
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Liver X Receptors
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Models, Biological
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Orphan Nuclear Receptors
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Polycyclic Aromatic Hydrocarbons / pharmacology*
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Polycyclic Aromatic Hydrocarbons / toxicity
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / genetics
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, Aryl Hydrocarbon / metabolism
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Receptors, Cytoplasmic and Nuclear / genetics
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic / drug effects
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Transcription, Genetic / genetics
Substances
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3-methlycholanthrene
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Benz(a)Anthracenes
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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Liver X Receptors
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NR1H3 protein, human
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Orphan Nuclear Receptors
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Polycyclic Aromatic Hydrocarbons
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RNA, Messenger
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RNA, Small Interfering
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Receptors, Aryl Hydrocarbon
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Receptors, Cytoplasmic and Nuclear
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SREBF1 protein, human
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Sterol Regulatory Element Binding Protein 1
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Transcription Factors