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The mycoestrogen zeranol at high dosage antagonizes transient receptor potential channel activities in 3T3 L1 cells

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TOXICOLOGY LETTERS
卷 344, 期 -, 页码 18-25

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2021.03.003

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Zeranol; TRP-V1 and-C6 antagonist; Adipocyte differentiation

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Recent research has indicated that exposure to environmental contaminants can lead to obesity and pose a health risk to the public. This study investigated the interaction between TRPs and specific food pollutants, finding that zeranol could enhance fat cell differentiation by antagonizing TRP-V1 and -C6 activities, leading to reduced calcium inflow and potentially promoting adipogenesis.
Recent findings have revealed that exposure to environmental contaminants may result in obesity and pose a health threat to the general public. As the activity of transient receptor potential channels (TRPs) plays a permissive role in adipogenesis, the interactions between TRPs and some food pollutants, i.e. bisphenol A, di (2-ethylhexyl) phthalate, zearalenone, and zeranol at 10 mu M were investigated in the present study. TRP-V1,-V3, -C4 and -C6 are reported to be differentially expressed in the adipocyte differentiation, and immunoblotting was performed to quantify changes in these TRPs affected by the pollutants. Our result indicated that the mycoestrogen zeranol or alpha-zearalanol suppressed the expression of the V1 and C6 isoforms. Subsequently, confocal microscopy was used to measure the calcium inflow repressed by zeranol from 0.1 mu M to 10 mu M. Oil Red O staining was used to determine the differentiation of 3T3 L1 preadipocytes. Zeranol could suppress the expression of TRP-V1 and -C6 protein and inhibit the associated flow of calcium into the cytosol of 3T3 L1 cells. Its IC50 value for inhibiting calcium inflow stimulated by 40 mu M capsaicin or 10 mu M GSK1702934A was estimated to be around 6 mu M. Reduced TRPV1 or -C6 activity might result in promoting adipogenesis. In conclusion, this study demonstrated that zeranol could potentiate fat cell differentiation through antagonizing TRP-V1 and -C6 activities. (C) 2021 Elsevier B.V. All rights reserved.

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