New progress in molecular toxicological mechanism of perfluorocarbons

Guo Lianghong, State Key Laboratory of environmental chemistry and ecotoxicology, research group of ecological environment research center, Chinese Academy of Sciences, has made new progress in the molecular toxicology mechanism of perfluorocarbons (PFCs) The relevant research results have been published in the international famous toxicology journal Archives of toxicology recently Figure 1: the molecular mechanism of PFCs up regulating the phosphorylation level of paxillin protein in HepG2 cells (source: Yang et al Arch Toxicol 2017, 91:1697 – 1707) PFCs are a new type of organic pollutants with high environmental persistence and bioaccumulation Environmental epidemiological studies revealed a high correlation between human PFCs exposure and a variety of adverse health effects Animal experiments showed that PFCs had hepatotoxicity, endocrine interference, embryotoxicity, reproductive toxicity, neurotoxicity and potential carcinogenicity However, the toxic mechanism of PFCs is not clear One of the reasons is that the target molecule, molecular initiation event (MIE) and adverse outcome pathway (AOP) of PFCs in vivo have not been fully revealed Guo Lianghong research group has long been engaged in the study of toxic effects and toxicological mechanisms of new persistent organic pollutants such as PFCs In view of the environmental health problems of PFCs, the research group has carried out a long-term and systematic study on the molecular mechanism of PFCs toxicity from different aspects such as molecular effect, cell effect, in vivo effect, theoretical calculation, etc In his work, the binding reaction of PFCs with three thyroid hormone transporters (HSA, TTR, TBG and FABP) was studied to evaluate the potential interference effect of pollutants on thyroid hormone and fatty acid transport in vivo (arch Toxicol., 2009; environ SCI Technol., 2013a, Toxicol., 2016) The binding reaction between PFCs and tr was studied, and the activation of TR mediated signal pathway in cells was studied The interference effect and mechanism of low dose exposure of PFCs on thyroid system of Xenopus laevis were revealed (arch Toxicol., 2015) The binding reaction of PFCs with peroxisome proliferator activated receptor γ (PPAR γ) was studied, and the activation effect of PPAR γ mediated signal channels in cells was studied (Toxicol Appl Pharmacol., 2014) In addition, the method of ligand receptor interaction based on SPR sensor was established, and the conformational changes and activation effects of estrogen receptor after binding with some PFCs were found (environ SCI Technol., 2013b) These results are of great significance to clarify the biological target molecules and initial molecular events of PFCs, and to reveal the molecular mechanism of toxic effects of PFCs Recently, the research team tried to find unknown target molecules of PFCs in vivo, so as to expand the study of the toxicological mechanism of PFCs The study group found that PFCs had a significant inhibitory effect on the activity of protein tyrosine phosphatase SHP2 through the method of electrochemical sensor screening By immunocoprecipitation, the researchers obtained shp2-pfcs complex from HepG2 cells exposed to PFCs, which directly confirmed that SHP2 enzyme is a new target molecule of PFCs in cells When PFCs enter the cells, they can bind to SHP2 enzyme and inhibit its activity, resulting in the abnormal increase of phosphorylation level of paxillin, a downstream substrate protein catalysed by the enzyme SHP2 is a very important protein tyrosine phosphatase, which is involved in the activation of multiple signaling pathways and plays an important role in the proliferation, invasion, metastasis and drug resistance of tumor cells The inhibition of the binding of PFCs to SHP2 may be the molecular initiating event, which further interferes with the subsequent normal physiological process regulated by SHP2, which may be one of the toxic mechanisms of PFCs This study provides a new way to reveal the molecular mechanism of toxicity of PFCs Paper link: 1 Arch Toxicol 2009: http://link.springer.com/article/10.1007% 2fs00204-008-0359-x 2 Environ SCI Technol 2013a: http://pubs.acs.org/doi/abs/10.1021/es4026722 3 Environ SCI Technol 2013b: http://pubs.acs.org/doi/abs/10.1021/es304030x 4 Toxicol Appl Pharmacol 2014: 016-1836-2 extended reading: PFCs, perfluorinated, waterproof In garment production, it is mainly used for the manufacture of outerwear In addition, PFCs are also used in tents, shower curtains and other products PFCs are harmful to the environment and human body, especially to the recycling of water and the reproduction of microorganisms in water.