Issue 11, 2019

Investigation of binding and activity of perfluoroalkyl substances to the human peroxisome proliferator-activated receptor β/δ

Abstract

Previously, perfluoroalkyl substances (PFASs) have been found to be associated with many adverse effects mediated by the peroxisome proliferator-activated receptor α (PPARα) and PPARγ. Here, we found another subtype of the peroxisome proliferator-activated receptors (PPARs); the PPARβ/δ mediated pathway might also be a potential adverse outcome pathway for PFASs. We investigated the direct binding and transcriptional activity of PFASs toward human PPARβ/δ, and further revealed the structure-binding and structure–activity relationship between PFASs and PPARβ/δ. The receptor binding experiment showed that their binding potency was dependent on the carbon chain length and the terminal functional group. For twelve perfluoroalkyl carboxylic acids (PFCAs), an inverted U-shaped relationship existed between the PPARβ/δ binding potency and the carbon chain length, with perfluorododecanoc acid (C12) showing the highest binding potency. The three perfluoroalkane sulfonic acids (PFSAs) exhibited a stronger binding potency than their PFCA counterparts. The two fluorotelomer alcohols (FTOHs) showed no binding potency. In receptor transcriptional activity assays, they enhanced the PPARβ/δ transcriptional activity. Their transcriptional activity was also related to the carbon chain length and the terminal functional group. Molecular docking analysis showed the PFASs fitted into the ligand binding pocket of PPARβ/δ with a binding geometry similar to a fatty acid.

Graphical abstract: Investigation of binding and activity of perfluoroalkyl substances to the human peroxisome proliferator-activated receptor β/δ

  • This article is part of the themed collection: PFAS

Supplementary files

Article information

Article type
Paper
Submitted
09 Maijs 2019
Accepted
02 Jūl. 2019
First published
10 Jūl. 2019

Environ. Sci.: Processes Impacts, 2019,21, 1908-1914

Investigation of binding and activity of perfluoroalkyl substances to the human peroxisome proliferator-activated receptor β/δ

C. Li, X. Ren, L. Cao, W. Qin and L. Guo, Environ. Sci.: Processes Impacts, 2019, 21, 1908 DOI: 10.1039/C9EM00218A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements