Two Thiophenes Compounds Are Partial Peroxisome Proliferator-Activated Receptor .ALPHA./.GAMMA. Dual Agonists

Zheng, Zhaohui; Yang, Yi; Shao, Huayi; Liu, Zongying; Lu, Xinhua; Yang, Xu; He, Xiaobo; Jiang, Wei; Jiang, Qin; Zhao, Bin; Zhang, Hua; Li, Zhuorong; Si, Shuyi

doi:10.1248/bpb.34.1631

Cited by 6 publications

(5 citation statements)

References 23 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the transiently transfected COS7 cells, luciferase activities increased approximately 8-fold when exposed to rosiglitazone, whereas rosiglitazone-induced (0.5 μM) luciferase production was inhibited by the known PPARG-antagonists GW9662 and BADGE (Table ). EC50 and IC50 for rosiglitazone and GW9662 (Table ) were comparable to previous studies using GAL4 systems. ,, BADGE exposure led to a similar decrease of luciferase activity as GW9662, although at higher exposure concentrations (Table B, Figure S3B). This is in accordance with previous studies that have characterized BADGE as a low-affinity antagonist. , Thus, the pbPPARG LRA appears to produce results comparable to those of previous studies.…”

Section: Resultssupporting

confidence: 85%

“…EC50 and IC50 for rosiglitazone and GW9662 (Table 1) were comparable to previous studies using GAL4 systems. 30,44,45 BADGE exposure led to a similar decrease of luciferase activity as GW9662, although at higher exposure concentrations (Table 1B, Figure S3B). This is in accordance with previous studies that have characterized BADGE as a low-affinity antagonist.…”

Section: ■ Results and Discussionmentioning

confidence: 75%

See 1 more Smart Citation

Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro

Routti

Lille-Langøy

Berg

et al. 2016

Environ. Sci. Technol.

View full text Add to dashboard Cite

We studied interactions between polar bear peroxisome proliferator-activated receptor gamma (pbPPARG) and selected compounds using a luciferase reporter assay and predictions through molecular docking. Furthermore, we studied adipogenesis by liver and adipose tissue extracts from a polar bear and three synthetic mixtures of contaminants in murine 3T3-L1 preadipocytes and polar bear adipose tissue-derived stem cells (pbASCs). PCB153 and p,p'-DDE antagonized pbPPARG, although their predicted receptor-ligand affinity was weak. PBDEs, tetrabromobisphenol A, and PCB170 had a weak agonistic effect on pbPPARG, while hexabromocyclododecane, bisphenol A, oxychlordane, and endosulfan were weak antagonists. pbPPARG-mediated luciferase activity was suppressed by synthetic contaminant mixtures reflecting levels measured in polar bear adipose tissue, as were transcript levels of PPARG and the PPARG target gene fatty acid binding protein 4 (FABP4) in pbASCs. Contaminant extracts from polar bear tissues enhanced triglyceride accumulation in murine 3T3-L1 cells and pbASCs, whereas triglyceride accumulation was not affected by the synthetic mixtures. Chemical characterization of extracts using nontarget methods revealed presence of exogenous compounds that have previously been reported to induce adipogenesis. These compounds included phthalates, tonalide, and nonylphenol. In conclusion, major legacy contaminants in polar bear adipose tissue exert antagonistic effects on PPARG, but adipogenesis by a mixture containing emerging compounds may be enhanced through PPARG or other pathways.

show abstract

Section: Resultssupporting

confidence: 85%

Section: ■ Results and Discussionmentioning

confidence: 75%

Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro

Routti

Lille-Langøy

Berg

et al. 2016

Environ. Sci. Technol.

View full text Add to dashboard Cite

show abstract

“…A stable transformed CLA1p-LUC HepG2 cell line was maintained in medium E (medium B supplemented with 600 g/ml G418). domain, LBD) and pBIND-LXR ␤ -LBD] were constructed as previously described ( 35 ). ABCA1, CLA-1 transcriptional activity assay, and pBIND-LXR ␣ /LXR ␤ -LBD/GAL4 chimera reporter assay were performed as previously described using ABCA1p-LUC HepG2 ( 20 ), CLA1p-LUC HepG2 ( 21 ), and HepG2 cells, respectively.…”

Section: Cell Culturesmentioning

confidence: 99%

Rutaecarpine suppresses atherosclerosis in ApoE−/− mice through upregulating ABCA1 and SR-BI within RCT

Yang

Liu

et al. 2014

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

Excessive accumulation of cholesterol in macrophages results in a transformation of the macrophage into foam cells and eventually causes atherosclerosis ( 1, 2 ). The pathogenic process represents a chronic and complicated interaction involving multiple factors. Reverse cholesterol transport (RCT) is a process by which extrahepatic (peripheral) cholesterol is returned to the liver for excretion in the bile and ultimately the feces, thus reducing the risk of atherosclerosis ( 3, 4 ). Although there have been great efforts in discovering drugs against atherosclerosis ( 5 ), the output has been unsatisfactory. Removal of excess cholesterol from macrophage foam cells is considered to be one of the therapeutic strategies ( 6 ). The crucial cellular transporters and receptors that relate to cholesterol effl ux include,

show abstract

“…As for the ABCA1 DR4 mutation plasmid, 13 it was generated using the ABCA1-promoter-pGL3 plasmid as a template and verified by DNA sequencing. The ABCA1 transcriptional activity assay 11 was carried out using ABCA1p-LUC HepG2 cells, whereas the ABCA1 DR4 element (a direct repeat of 2 hexameric-binding motifs spaced by 4 nucleotides) mutation plasmid and pBIND-NR-LBD/GAL4 chimera reporter assays 14,15 were performed using HepG2 cells. E17241 was added to the cells at specific concentrations, and 24 hours later, the luciferase activity of these cells was detected.…”

Section: Methodsmentioning

confidence: 99%

E17241 as a Novel ABCA1 (ATP-Binding Cassette Transporter A1) Upregulator Ameliorates Atherosclerosis in Mice

Yang¹,

Liu²,

Han³

et al. 2021

ATVB

Self Cite

View full text Add to dashboard Cite

Objective: Reverse cholesterol transport, removing excess cholesterol from peripheral tissues, is an important therapeutic target for atherosclerosis treatment. In this study, we propose a new small molecule, E17241, that may be used to treat atherosclerosis by promoting reverse cholesterol transport via ABCA1 (ATP-binding cassette transporter A1) upregulation. Approach and Results: E17241 (4-(1,3-dithiolan-2-yl)-N-(3-hydroxypyridin-2-yl)benzamide) was first identified as an ABCA1 upregulator using a cell-based reporter assay. E17241 significantly increases the mRNA and protein expression levels of ABCA1 in both hepatic cells and macrophages. It promotes cholesterol efflux to apo AI in macrophage cells, and this effect depends on ABCA1. It also decreases total cholesterol content in Ox-LDL (oxidized low-density lipoprotein) loading macrophage cells. E17241 treatment increases the content of 3 H-labeled cholesterol in the feces of male C57BL/6J mice intraperitoneally injected with 3H-cholesterol-labeled macrophage J774 cells, indicating that it could promote in vivo macrophage reverse cholesterol transport. Compared with the western diet group (western diet–fed male ApoE −/− mice), the E17241 group (western diet+E17241 treatment) shows decreased plasma cholesterol, liver cholesterol, and triglyceride levels, with increased fecal cholesterol content. Importantly, E17241 reduces atherosclerotic lesion areas in the en face aorta and aortic sinus while increasing ABCA1 protein levels in both liver and macrophages. Human proteome microarray, coimmunoprecipitation, and other assays demonstrate that PKCζ (protein kinase C zeta) is a binding target of E17241, and this small molecule increases ABCA1 expression in macrophages via the PKCζ-NR (nuclear receptor) pathway. Conclusions: E17241 may be developed as a new lead or drug candidate for the treatment of atherosclerosis by upregulating ABCA1.

show abstract

Two Thiophenes Compounds Are Partial Peroxisome Proliferator-Activated Receptor .ALPHA./.GAMMA. Dual Agonists

Cited by 6 publications

References 23 publications

Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro

Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro

Rutaecarpine suppresses atherosclerosis in ApoE−/− mice through upregulating ABCA1 and SR-BI within RCT

E17241 as a Novel ABCA1 (ATP-Binding Cassette Transporter A1) Upregulator Ameliorates Atherosclerosis in Mice

Contact Info

Product

Resources

About