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高剂量的真菌雌激素玉米赤霉醇会拮抗 3T3 L1 细胞中的瞬时受体电位通道活性。

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

机构信息

Biochemistry Programme, School of Life Sciences, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.

Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.

出版信息

Toxicol Lett. 2021 Jun 15;344:18-25. doi: 10.1016/j.toxlet.2021.03.003. Epub 2021 Mar 6.

Abstract

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 μM 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 α-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 μM to 10 μM. 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 IC value for inhibiting calcium inflow stimulated by 40 μM capsaicin or 10 μM GSK1702934A was estimated to be around 6 μM. Reduced TRP-V1 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.

摘要

最近的研究结果表明,环境污染物的暴露可能导致肥胖,并对公众健康构成威胁。瞬时受体电位通道(TRP)的活性在脂肪生成中起着允许作用,因此本研究调查了 TRP 与一些食物污染物(即双酚 A、邻苯二甲酸二(2-乙基己基)酯、玉米赤霉烯酮和泽那醇)在 10μM 时的相互作用。据报道,TRP-V1、-V3、-C4 和 -C6 在脂肪细胞分化中表达不同,通过免疫印迹来量化这些受污染物影响的 TRP 的变化。我们的结果表明,真菌雌激素玉米赤霉烯酮或α-玉米赤霉烯醇抑制了 V1 和 C6 同工型的表达。随后,使用共聚焦显微镜测量了泽那醇从 0.1μM 到 10μM 抑制钙内流的情况。油红 O 染色用于确定 3T3 L1 前脂肪细胞的分化。泽那醇可以抑制 TRP-V1 和 -C6 蛋白的表达,并抑制 3T3 L1 细胞细胞质中钙的相关内流。其抑制 40μM 辣椒素或 10μM GSK1702934A 刺激的钙内流的 IC 值估计约为 6μM。TRP-V1 或 -C6 活性的降低可能导致脂肪生成的促进。总之,本研究表明,泽那醇通过拮抗 TRP-V1 和 -C6 活性来增强脂肪细胞分化。

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