es7b02055_si_001.pdf (1.76 MB)
Structure-Dependent Hematological Effects of Per- and Polyfluoroalkyl Substances on Activation of Plasma Kallikrein–Kinin System Cascade
journal contribution
posted on 2017-07-26, 00:00 authored by Qian S. Liu, Yuzhen Sun, Guangbo Qu, Yanmin Long, Xingchen Zhao, Aiqian Zhang, Qunfang Zhou, Ligang Hu, Guibin JiangPer-
and polyfluoroalkyl substances (PFASs) are a global concern
because of their ubiquitous occurrence and high persistence in human
blood, and increasing amounts of unidentified fluorinated compounds
are now becoming new exposure issues. This study aims to investigate
the structure-related effects of PFASs on the activation of the plasma
kallikrein-kinin system (KKS). The effects of 20 PFASs and the related
long-chain aliphatic compounds were screened, and their binding affinities
for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were
evaluated by molecular docking analysis. PFASs were demonstrated to
activate the KKS in a structure-dependent mode. More specifically,
PFASs with longer carbon chain length, higher fluorine atom substitution
degree, and terminal acid group exhibited relatively higher activities
in activating the KKS. The binding affinities of PFASs with FXII determined
their capabilities for inducing KKS activation. The alternative binding
modes of PFASs with FXII, together with van der Waals and hydrogen
bonds, specifically accommodated the distinctive chemical structures.
To our knowledge, PFASs, for the first time, were found to induce
the activation of the KKS in plasma, and their chemical structure-related
effects would be extremely important for risk assessment on emerging
PFASs in addition to the listing in Stockholm Convention.