PMID- 16730733 OWN - NLM STAT- MEDLINE DCOM- 20070410 LR - 20181201 IS - 0021-9150 (Print) IS - 0021-9150 (Linking) VI - 191 IP - 1 DP - 2007 Mar TI - Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element. PG - 11-21 AB - ATP-binding cassette transporters (ABC) G1 and ABCA1 are membrane cholesterol transporters and have been implicated to mediate cholesterol efflux from cells in the presence of high density lipoproteins and its major protein constituent apolipoprotein A-I, respectively. We previously demonstrated that unsaturated fatty acids suppress the stimulatory effects of oxysterols and retinoids on ABCA1 gene transcription. We here demonstrate that unsaturated fatty acids significantly suppress the stimulatory effects of oxysterols and retinoids on the expression of ABCG1 mRNA and protein and the activity of the wild-type human ABCG1 promoter as well as ABCA1. Mutation or deletion of the DR4 element within the ABCG1 or ABCA1 promoters, to which the transcriptional inducers LXR and RXR bind, abolished the suppressive effects of unsaturated fatty acids. Our observations provide the first evidence that unsaturated fatty acids suppress ABCG1 gene expression by a mechanism which involves the binding of LXR/RXR to the promoters. Suppression of both the ABCA1 and ABCG1 genes may indicate that unsaturated fatty acids suppress not only cholesterol efflux to apoA-I and thereby nascent HDL formation but also HDL-dependent cholesterol efflux from vascular cells. FAU - Uehara, Yoshinari AU - Uehara Y AD - Department of Neurology and Healthcare, Fukuoka University Hospital, 7-45-1 Nanakuma, Jonan-ku, 814-0180 Fukuoka, Japan. ueharay@fukuoka-u.ac.jp FAU - Miura, Shin-ichiro AU - Miura S FAU - von Eckardstein, Arnold AU - von Eckardstein A FAU - Abe, Satomi AU - Abe S FAU - Fujii, Akihiro AU - Fujii A FAU - Matsuo, Yoshino AU - Matsuo Y FAU - Rust, Stephan AU - Rust S FAU - Lorkowski, Stefan AU - Lorkowski S FAU - Assmann, Gerd AU - Assmann G FAU - Yamada, Tatsuo AU - Yamada T FAU - Saku, Keijiro AU - Saku K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060530 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (ABCA1 protein, human) RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Cholesterol, LDL) RN - 0 (DNA-Binding Proteins) RN - 0 (Fatty Acids, Unsaturated) RN - 0 (Lipoproteins) RN - 0 (Liver X Receptors) RN - 0 (Orphan Nuclear Receptors) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Retinoid X Receptors) SB - IM MH - ATP Binding Cassette Transporter 1 MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/genetics/*metabolism MH - Animals MH - Cell Line MH - Cholesterol, LDL/metabolism MH - DNA-Binding Proteins/physiology MH - Fatty Acids, Unsaturated/*physiology MH - Gene Expression Regulation/*physiology MH - Humans MH - Lipoproteins/genetics/*metabolism MH - Liver X Receptors MH - Mice MH - Orphan Nuclear Receptors MH - Point Mutation MH - Promoter Regions, Genetic/*physiology MH - Receptors, Cytoplasmic and Nuclear/physiology MH - Retinoid X Receptors/physiology EDAT- 2006/05/30 09:00 MHDA- 2007/04/11 09:00 CRDT- 2006/05/30 09:00 PHST- 2005/05/06 00:00 [received] PHST- 2006/04/11 00:00 [revised] PHST- 2006/04/13 00:00 [accepted] PHST- 2006/05/30 09:00 [pubmed] PHST- 2007/04/11 09:00 [medline] PHST- 2006/05/30 09:00 [entrez] AID - S0021-9150(06)00212-7 [pii] AID - 10.1016/j.atherosclerosis.2006.04.018 [doi] PST - ppublish SO - Atherosclerosis. 2007 Mar;191(1):11-21. doi: 10.1016/j.atherosclerosis.2006.04.018. Epub 2006 May 30.