Disclosing Environmental Ligands of L-FABP and PPARγ: Should We Re-evaluate the Chemical Safety of Hydrocarbon Surfactants?,Environmental Science & Technology

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Disclosing Environmental Ligands of L-FABP and PPARγ: Should We Re-evaluate the Chemical Safety of Hydrocarbon Surfactants?
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2023-08-01 , DOI: 10.1021/acs.est.3c02898
Yufeng Gong ₁ , Diwen Yang ₁ , Jiabao Liu _{1,

2} , Holly Barrett ₁ , Jianxian Sun ₁ , Hui Peng _{1,

3}

Affiliation

Chemical contaminants can cause adverse effects by binding to the liver-fatty acid binding protein (L-FABP) and peroxisome proliferator-activated nuclear receptor γ (PPARγ), which are vital in lipid metabolism. However, the presence of numerous compounds in the environment has hindered the identification of their ligands, and thus only a small portion have been discovered to date. In this study, protein Affinity Purification with Nontargeted Analysis (APNA) was employed to identify the ligands of L-FABP and PPARγ in indoor dust and sewage sludge. A total of 83 nonredundant features were pulled-out by His-tagged L-FABP as putative ligands, among which 13 were assigned as fatty acids and hydrocarbon surfactants. In contrast, only six features were isolated when His-tagged PPARγ LBD was used as the protein bait. The binding of hydrocarbon surfactants to L-FABP and PPARγ was confirmed using both recombinant proteins and reporter cells. These hydrocarbon surfactants, along with >50 homologues and isomers, were detected in dust and sludge at high concentrations. Fatty acids and hydrocarbon surfactants explained the majority of L-FABP (57.7 ± 32.9%) and PPARγ (66.0 ± 27.1%) activities in the sludge. This study revealed hydrocarbon surfactants as the predominant synthetic ligands of L-FABP and PPARγ, highlighting the importance of re-evaluating their chemical safety.

中文翻译：

公开L-FABP和PPARγ的环境配体：我们是否应该重新评估碳氢表面活性剂的化学安全性？

化学污染物可通过与肝脏脂肪酸结合蛋白 (L-FABP) 和过氧化物酶体增殖物激活核受体 γ (PPARγ) 结合而造成不利影响，这两种物质对于脂质代谢至关重要。然而，环境中存在的多种化合物阻碍了其配体的鉴定，因此迄今为止仅发现了一小部分。在这项研究中，采用蛋白A亲和纯化结合N定向分析（APNA）来鉴定室内灰尘和污水污泥中L-FABP和PPARγ的配体。His 标记的 L-FABP 总共提取出 83 个非冗余特征作为假定配体，其中 13 个被指定为脂肪酸和碳氢化合物表面活性剂。相比之下，当使用 His 标记的 PPARγ LBD 作为蛋白质诱饵时，仅分离出 6 个特征。使用重组蛋白和报告细胞证实了碳氢化合物表面活性剂与 L-FABP 和 PPARγ 的结合。这些碳氢化合物表面活性剂以及超过 50 种同系物和异构体在灰尘和污泥中以高浓度被检测到。脂肪酸和碳氢表面活性剂解释了污泥中 L-FABP (57.7 ± 32.9%) 和 PPARγ (66.0 ± 27.1%) 活性的大部分。这项研究揭示了烃类表面活性剂是 L-FABP 和 PPARγ 的主要合成配体，强调了重新评估其化学安全性的重要性。

更新日期：2023-08-01

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