RRC ID 67930
Author Cui H, Okuhira K, Ohoka N, Naito M, Kagechika H, Hirose A, Nishimaki-Mogami T.
Title Tributyltin chloride induces ABCA1 expression and apolipoprotein A-I-mediated cellular cholesterol efflux by activating LXRα/RXR.
Journal Biochem Pharmacol
Abstract Organotins, including tri-butyltin chloride (TBTC), are widely used in agricultural and chemical industries and cause persistent and widespread pollution. TBTC has been shown to activate nuclear receptor retinoid X receptor (RXR)/PPARγ signaling by interacting with RXR to modulate adipogenesis. However, whether TBTC affects liver X receptor (LXR)/RXR activity and subsequently the expression of cholesterol mobilizing genes is not known. In this study, we evaluated the ability of TBTC to activate LXR/RXR and ABC transporter A1 (ABCA1) expression. ABCA1 plays a critical role in HDL generation, maintaining cholesterol homeostasis, and cholesterol accumulation-induced diseases, such as atherosclerosis and pancreatic islet dysfunction. In a reporter gene assay, TBTC activated LXRα/RXR but not LXRβ/RXR. In mouse macrophage RAW264 cells, TBTC activated the ABCA1 promoter in an LXR-responsive element dependent manner and increased ABCA1 mRNA expression. TBTC augmented ABCA1 protein levels and apolipoprotein A-I-dependent cellular cholesterol efflux (HDL generation). The LXR-target fatty acid synthase and Spα mRNA levels were also increased by TBTC exposure. We conclude that TBTC has the ability to activate permissive LXRα/RXR signaling and thereby modulate cellular cholesterol efflux.
Volume 81(6)
Pages 819-24
Published 2011-3-15
DOI 10.1016/j.bcp.2010.12.023
PII S0006-2952(11)00010-4
PMID 21219878
MeSH ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters / biosynthesis* Animals Apolipoprotein A-I / physiology* COS Cells Cell Line Cell Membrane / drug effects Cell Membrane / metabolism* Chlorocebus aethiops Cholesterol / metabolism* Gene Expression Regulation Liver X Receptors Mice Orphan Nuclear Receptors / agonists Orphan Nuclear Receptors / metabolism* Receptors, Retinoic Acid / agonists Receptors, Retinoic Acid / metabolism Trialkyltin Compounds / toxicity*
IF 4.96
Human and Animal Cells RAW 264(RCB0535)