Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element

Uehara, Yoshio; Miura, Shin-ichiro; Eckardstein, Arnold von; Abe, Satomi; Fujii, Akihiro; Matsuo, Yoshino; Rust, Stephan; Lorkowski, Stefan; Assmann, Gerd; Yamada, Tatsuo; Saku, Keijiro

doi:10.1016/j.atherosclerosis.2006.04.018

Cited by 109 publications

(104 citation statements)

References 33 publications

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“…Human ABCG1 promoter constructs-Firefly luciferase reporter constructs were generated by PCR amplification of a 1141-bp fragment of human ABCG1 promoter ( 1104/ 37) and then subcloned with pGL3-Basic vectors (Promega, Madison, WI), as described previously 22) . Site-directed mutagenesis-Mutant plasmids were obtained for human ABCG1 promoter using the QuickChange® Site-Directed Mutagenesis Kit (Stratagene, La Jolla, CA) and each of the following double-stranded oligonucleotides.…”

Section: Reporter Plasmid Constructsmentioning

confidence: 99%

“…ABCG1 promoter 257T G mutation: ABCG1 257T G sense, 5´-CGC CCA GTG ACT TGG GAG GGA ACA GAA CTG-3´ and ABCG1 257T G antisense, 5´-CAG TTC TGT TCC CTC CCA AGT CAC TGG GCG-3´. The setting for mutagenesis was selected according to the manufacturer's protocol as described previously 22) . The identity of all DNA constructs was confirmed by DNA sequencing.…”

Section: Reporter Plasmid Constructsmentioning

confidence: 99%

“…The ABCG1 gene possesses a promoter upstream of exon 1 and another intron promoter, which encodes several transcripts [19][20][21] . Our previous study demonstrated that ligands for liver-Xreceptor (LXR) dramatically increase the activity of the ABCG1 promoter located upstream of exon 1 22) ; therefore, a ABCG1 nucleotide polymorphism in this LXR-responsive promoter is examined.…”

Section: Introductionmentioning

confidence: 99%

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Genotypic Effect of ABCG1 Gene Promoter -257T>G Polymorphism on Coronary Artery Disease Severity in Japanese Men

Furuyama

Uehara

Zhang

et al. 2009

JAT

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Aim: ATP-binding cassette transporter G1 (ABCG1) is a cholesterol transporter that plays a role in cholesterol efflux in the presence of high-density lipoprotein (HDL). Moreover, HDL-mediated cholesterol efflux is increased in cultured ABCG1 overexpressed cells; however, the physiological roles of ABCG1 and its contribution to atherosclerosis in humans remain unclear. Methods: The effect of ABCG1 257T G mutation on transcription activity was determined by a reporter assay. One hundred nine Japanese men with coronary artery disease (CAD) were analyzed. ABCG1 257T G polymorphism was assessed by mutation-selective PCR methods to identify T/T, T/G, and G/G genotypes. Results:The reporter assay showed that ABCG1 transcription activity was significantly lower (p 0.01) in the G allele of 257T G polymorphism compared with that in the T allele. Clinically, there were no significant differences in serum triglyceride and total, LDL, and HDL cholesterol levels, or other risk factors. Logistic regression analysis revealed significant additive and dominant effects on the frequency of patients with multi-vessel disease compared with single-vessel disease

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Section: Reporter Plasmid Constructsmentioning

confidence: 99%

Section: Reporter Plasmid Constructsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genotypic Effect of ABCG1 Gene Promoter -257T>G Polymorphism on Coronary Artery Disease Severity in Japanese Men

Furuyama

Uehara

Zhang

et al. 2009

JAT

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“…This finding explained the possible mechanism for why danthron decreased TC content. Nevertheless, danthron as www.chinaphar.com Zhou R et al Acta Pharmacologica Sinica npg an antagonist of the retinoic X receptor α/liver X receptor α (RXRα/LXRα) heterodimer may negatively affect the expressions of ABCA1 and ABCG1 [21,[29][30][31] . Thus, the effects of danthron on the ABCA1 and ABCG1 gene expressions seem to be contradictory and complicated.…”

Section: Discussionmentioning

confidence: 99%

Danthron activates AMP-activated protein kinase and regulates lipid and glucose metabolism in vitro

Zhou

Chen

et al. 2013

Acta Pharmacol Sin

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Aim: To discover the active compound on AMP-activated protein kinase (AMPK) activation and investigate the effects of the active compound 1,8-dihydroxyanthraquinone (danthron) from the traditional Chinese medicine rhubarb on AMPK-mediated lipid and glucose metabolism in vitro. Methods: HepG2 and C2C12 cells were used. Cell viability was determined using MTT assay. Real-time PCR was performed to measure the gene expression. Western blotting assay was applied to investigate the protein phosphorylation level. Enzymatic assay kits were used to detect the total cholesterol (TC), triglyceride (TG) and glucose contents. Results: Danthron (0.1, 1, and 10 µmol/L) dose-dependently promoted the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) in both HepG2 and C2C12 cells. Meanwhile, danthron treatment significantly reduced the lipid synthesis related sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthetase (FAS) gene expressions, and the TC and TG levels. In addition, danthron treatment efficiently increased glucose consumption. The actions of danthron on lipid and glucose metabolism were abolished or reversed by co-treatment with the AMPK inhibitor compound C. Conclusion: Danthron effectively reduces intracellular lipid contents and enhanced glucose consumption in vitro via activation of AMPK signaling pathway.

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“…Altogether, this transforms the HDL 3 particles into larger and less dense HDL 2 particles. Like ABCA1, this transporter is regulated by LXR and hence suppressed by unsaturated fatty acids at the transcriptional level (Uehara et al 2007) so that the production of larger HDL 2 is compromised. In addition, the conversion of HDL 2 into HDL 3 is enhanced in diabetic dyslipidemia by increased activities of CETP and hepatic lipase: First, the transfer rate of cholesteryl esters from HDL to VLDL in normal individuals depends on the concentration of CE acceptors, that is, VLDL particles, but not on CETP activity (Mann et al 1991).…”

Section: Hdl Metabolism Subclasses and Catabolismmentioning

confidence: 99%

HDLs, Diabetes, and Metabolic Syndrome

Vollenweider

Eckardstein

Widmann

2014

High Density Lipoproteins

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The prevalence of type 2 diabetes mellitus and of the metabolic syndrome is rising worldwide and reaching epidemic proportions. These pathologies are associated with significant morbidity and mortality, in particular with an excess of cardiovascular deaths. Type 2 diabetes mellitus and the cluster of pathologies including insulin resistance, central obesity, high blood pressure, and hypertriglyceridemia that constitute the metabolic syndrome are associated with low levels of HDL cholesterol and the presence of dysfunctional HDLs. We here review the epidemiological evidence and the potential underlying mechanisms of this association. We first discuss the well-established association of type 2 diabetes mellitus and insulin resistance with alterations of lipid metabolism and how these alterations may lead to low levels of HDL cholesterol and the occurrence of dysfunctional HDLs. We then present and discuss the evidence showing that HDL modulates insulin sensitivity, insulin-independent glucose uptake, insulin secretion, and beta cell survival. A dysfunction in these actions could play a direct role in the pathogenesis of type 2 diabetes mellitus.

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Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element

Cited by 109 publications

References 33 publications

Genotypic Effect of ABCG1 Gene Promoter -257T>G Polymorphism on Coronary Artery Disease Severity in Japanese Men

Genotypic Effect of ABCG1 Gene Promoter -257T>G Polymorphism on Coronary Artery Disease Severity in Japanese Men

Danthron activates AMP-activated protein kinase and regulates lipid and glucose metabolism in vitro

HDLs, Diabetes, and Metabolic Syndrome

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