A possible mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons.

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.

• Authors: Shunsuke Iwano, Manabu Nukaya, Tetsuya Saito, Fumie Asanuma, Tetsuya Kamataki
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 335 Issue 1 Pg. 220-6 (Sep 16 2005) ISSN: 0006-291X [Print] United States
• PMID: 16061200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-methlycholanthrene
• Benz(a)Anthracenes
• CCAAT-Enhancer-Binding Proteins
• DNA-Binding Proteins
• Liver X Receptors
• NR1H3 protein, human
• Orphan Nuclear Receptors
• Polycyclic Aromatic Hydrocarbons
• RNA, Messenger
• RNA, Small Interfering
• Receptors, Aryl Hydrocarbon
• Receptors, Cytoplasmic and Nuclear
• SREBF1 protein, human
• Sterol Regulatory Element Binding Protein 1
• Transcription Factors

Topics

• Arteriosclerosis (chemically induced, genetics, metabolism)
• Benz(a)Anthracenes (pharmacology, toxicity)
• CCAAT-Enhancer-Binding Proteins (genetics, metabolism)
• Cell Line, Tumor
• DNA-Binding Proteins (genetics, metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Liver X Receptors
• Models, Biological
• Orphan Nuclear Receptors
• Polycyclic Aromatic Hydrocarbons (pharmacology, toxicity)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Receptors, Aryl Hydrocarbon (genetics, metabolism)
• Receptors, Cytoplasmic and Nuclear (genetics)
• Sterol Regulatory Element Binding Protein 1
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic (drug effects, genetics)