Activation of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPARγ1) by Semi-Volatile Compounds (SVOCs) and Chemical Mixtures in Indoor Dust.
Activation of Human Peroxisome Proliferator-Activated Nuclear Receptors (PPARγ1) by Semi-Volatile Compounds (SVOCs) and Chemical Mixtures in Indoor Dust.
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DOI：
10.1021/acs.est.5b01523
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发表时间：
2015-08-18
影响因子：
11.4
通讯作者：
Stapleton HM
中科院分区：
文献类型：
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作者：
Fang M;Webster TF;Stapleton HM
最近，我们报道了几种半挥发性化合物（SVOCs）是人过氧化物酶体增殖物激活核受体γ 1（PPARγ1）的竞争性配体。我们还观察到在给药介质中浓度为3 mg粉尘/mL的从室内粉尘中提取的化学品的显著结合。为了跟进该研究，使用市售报告基因测定（GeneBLAzer PPARγ1 non-DA Assay，Invitrogen）来研究30种常见SVOC（例如，溴化阻燃剂、有机磷酸盐和邻苯二甲酸盐）和室内灰尘提取物。28种SVOC或其代谢产物被证实或首次被发现是弱或中度的PPARγ1激动剂。我们还观察到激活15 25粉尘提取物检查。在某些情况下，活化高达阳性对照（罗格列酮）活化的50%。此外，从该报告基因测定收集的数据与我们之前对相同粉尘提取物进行的配体结合测定之间存在显著的正相关性（r = 0.7，p < 0.003）。我们的研究结果表明，许多SVOC普遍存在于室内灰尘，或其代谢产物，是可能的PPARγ1激动剂。此外，在环境相关水平的室内灰尘中存在的化学混合物可以在转染的细胞培养系统中激活人PPARγ1，需要进一步研究以确定驱动这种活性的主要化学物质。
Recently, we reported that several semi-volatile compounds (SVOCs) were competitive ligands for human peroxisome proliferator-activated nuclear receptor gamma (PPARγ1). We also observed significant binding from chemicals extracted from house dust at a concentration of 3 mg dust/mL in the dosing medium. To follow up on this study, a commercially available reporter gene assay (GeneBLAzer PPARγ1 non-DA Assay, Invitrogen) was used to investigate the PPARγ1 activation by 30 common SVOCs (e.g., brominated flame retardants, organophosphates, and phthalates) and in house dust extracts. Twenty-eight SVOCs or their metabolites were either confirmed or for the first time were found to be weak or moderate PPARγ1 agonists. We also observed activation in 15 of 25 dust extracts examined. In some cases, activation was as high as 50% of the activation of the positive control (rosiglitazone). Furthermore, there was a significant and positive correlation (r = 0.7, p < 0.003) between data collected from this reporter assay and our previous ligand binding assay tested on the same dust extracts. Our results suggest that many SVOCs ubiquitous in house dust, or their metabolites, are possible PPARγ1 agonists. Also, chemical mixtures present in house dust at environmentally relevant levels can activate human PPARγ1 in a transfected cell culture system, and further research is needed to identify the primary chemical(s) driving this activity.