Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Guangdong-Hong Kong Joint Laboratory for Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Environ Sci Technol. 2024 Sep 17;58(37):16258-16268. doi: 10.1021/acs.est.4c03053. Epub 2024 Aug 15.
Perfluorohexanesulfonic acid (PFHxS), an emerging short-chain per- and polyfluoroalkyl substance, has been frequently detected in aquatic environments. Adverse outcome pathway studies have shown that perfluorinated compounds impair lipid homeostasis through peroxisome proliferator activated receptors (PPARs). However, many of these studies were performed at high concentrations and may thus be a result of overt toxicity. To better characterize the molecular and key events of PFHxS to biota, early life-stage zebrafish () were exposed to concentrations detected in the environment (0.01, 0.1, 1, and 10 μg/L). Lipidomic and transcriptomic evaluations were integrated to predict potential molecular targets. PFHxS significantly impaired lipid homeostasis by the dysregulation of glycerophospholipids, fatty acyls, glycerolipids, sphingolipids, prenol lipids, and sterol lipids. Informatic analyses of the lipidome and transcriptome indicated alterations of the PPAR signaling pathway, with downstream changes to retinol, linoleic acid, and glycerophospholipid metabolism. To assess the role of PPARs, potential binding of PFHxS to PPARs was predicted and animals were coexposed to a PPAR antagonist (GW6471). Molecular simulation indicated PFHxS had a 27.1% better binding affinity than oleic acid, an endogenous agonist of PPARα. Antagonist coexposures rescued impaired glycerophosphocholine concentrations altered by PFHxS. These data indicate PPARα activation may be an important molecular initiating event for PFHxS.
全氟己烷磺酸（PFHxS）是一种新兴的短链全氟和多氟烷基物质，已在水生环境中频繁检出。 不良结局途径研究表明，全氟化合物通过过氧化物酶体增殖物激活受体（PPARs）破坏脂质稳态。 然而，许多这些研究是在高浓度下进行的，因此可能是由于明显的毒性所致。 为了更好地描述 PFHxS 对生物的分子和关键事件，早期生活阶段的斑马鱼（）暴露于环境中检测到的浓度（0.01、0.1、1 和 10 μg/L）。 对脂质组学和转录组学的评估进行了整合，以预测潜在的分子靶标。 PFHxS 通过甘油磷脂、脂肪酸、甘油酯、鞘脂、prenol 脂质和固醇脂质的失调显著破坏了脂质稳态。 脂质组学和转录组学的信息分析表明，PPAR 信号通路发生改变，视黄醇、亚油酸和甘油磷脂代谢发生下游变化。 为了评估 PPARs 的作用，预测了 PFHxS 与 PPARs 的潜在结合，并对动物进行了 PPAR 拮抗剂（GW6471）的共暴露。 分子模拟表明，PFHxS 与 PPARα 的内源性激动剂油酸的结合亲和力要好 27.1%。 拮抗剂共暴露挽救了 PFHxS 改变的甘油磷酸胆碱浓度受损。 这些数据表明，PPARα 的激活可能是 PFHxS 的一个重要的分子起始事件。
