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    Home > Biochemistry News > Biotechnology News > Advances in the mechanism by which PFCs produce toxic effects: SHP2 enzyme is a new target molecule of PFCs in cells.

    Advances in the mechanism by which PFCs produce toxic effects: SHP2 enzyme is a new target molecule of PFCs in cells.

    • Last Update: 2020-09-04
    • Source: Internet
    • Author: User
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    Guo Lianghong' research team at the National Key Laboratory of Environmental Chemistry and Ecotoxicology at the Center for Environmental Chemistry and Ecotoxicology of the Chinese Academy of Sciences has made new progress in molecular toxicology mechanisms of perfluorocarbons (PFCs), the results of which were published recently in the International Journal of Toxicology, Yang et al. Arch.Toxicol.2017, 91:1697-1707).
    PFCs are a widely watched new type of organic pollutant with high environmental persistence and bioa cumulativeity.
    environmental epidemiology reveals a high correlation between human PFCs exposure and a variety of adverse health effects.
    animal experiments show that PFCs have hepatotoxicity, endocrine interference, embryonic toxicity, reproductive toxicity, neurotoxicity and potential carcinogenicity.
    , however, the toxicity mechanism for PFCs is not yet clear.
    one of the reasons for this is that PFCs' target molecules, molecular start-up events (MEEs) and harmful outcome path paths (AOPs) in organisms have not yet been fully revealed.
    Guo Lianghong Research Group has long been engaged in PFCs and other new popsy toxic effects and toxicological mechanisms.
    the environmental health problems of PFCs, the research group carried out a long-term and systematic study on the molecular mechanism of PFCs toxicity from different levels, such as molecular action, cell effect, living effect and theoretical calculation.
    in its work, the binding reaction of PFCs to three thyroid hormone transport proteins, HSA, TTR, TBG, and fatty acid transport protein FABP, was studied to assess the potential interference effects of pollutants on the transport of thyroid hormones and fatty acids in the body.
    the binding reaction between PFCs and thyroid hormone-subject TR, the activation effect of TR-mediated signaling channels in cells, and the interference effect of low-dose exposure PFCs on the model biological African claw thyroid system and its mechanism of action were revealed.
    the binding reaction of PFCs to peroxidase proliferators activating the subject gamma (PPAR gamma) was studied, and the activation effect of PPAR gamma-mediated signal channels in cells (Toxicol.Appl.Pharmacol., 2014).
    also established a ligation-sensor interaction study based on surface plasma resonance sensors, and found that estrogen-like subjects combined with some PFCs have mechanism changes and activation effects (Environ.Sci Technol., 2013b).
    the above results are of great significance to clarify the bio-target molecules and starting molecular events of PFCs and to reveal the molecular mechanisms of PFCs' toxic effects.
    recently, the team tried to expand the toxicological mechanisms of PFCs by looking for molecules that are unknown in organisms.
    , the research team used electrochemical sensor screening to find that PFCs had a significant inhibitory effect on the activity of the protein tyrosine phosphatase SHP2.
    by immunopopulation, the researchers captured the compound of SHP2-PFCs from PFCs-exposed HepG2 cells, directly confirming that the SHP2 enzyme is a new target molecule in the cells of PFCs.
    PFCs enter the cell, they bind to and inhibit the activity of the SHP2 enzyme, resulting in an abnormal increase in phosphorylation levels of paxillin, the downstream substrate protein catalyzed by the enzyme.
    SHP2 is a very important protein tyrosine phosphatase, involved in the activity of many signaling path pathlines, in tumor cell proliferation, invasion, metastasis and drug resistance have played an important role.
    binding inhibition of PFCs and SHP2 enzymes may become a molecular starting event, further interfering with the subsequent normal physiological processes of SHP2 enzyme regulation, which may be one of the mechanisms by which PFCs produce toxic effects.
    this study provides a new way of thinking to reveal the molecular mechanism of PFCs toxicity.
    above research work has been the Chinese Academy of Sciences pilot special B and the National Fund Committee project support.
    .
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