Triclosan is a mitochondrial uncoupler in live zebrafish.

Triclosan is a mitochondrial uncoupler in live zebrafish.
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DOI:
10.1002/jat.3311
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发表时间:
2016-12
影响因子:
3.3
通讯作者:
Gosse, Julie A.
Gosse, Julie A.
中科院分区:
医学4区
文献类型:
--
作者:
Shim, Juyoung;Weatherly, Lisa M.;Luc, Richard H.;Dorman, Maxwell T.;Neilson, Andy;Ng, Ryan;Kim, Carol H.;Millard, Paul J.;Gosse, Julie A.

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三氯生(TCS)是一种合成抗菌剂,以毫摩尔浓度用于许多消费品。由于暴露,TCS已在人体中广泛检测到。我们最近发现,TCS是一种质子离子载体线粒体解偶联剂在多种类型的活细胞。在这里,我们提出了新的数据表明,TCS也是一个线粒体解偶联剂在一个活的有机体:24小时后受精斑马鱼胚胎。这些实验使用修改为双向温度控制的Seahorse Bioscience XFe 96胞外通量分析仪进行,使用XF 96球形板定位并测量每孔一个斑马鱼胚胎。使用这种方法,在急性暴露于TCS后,基础耗氧率(OCR)增加,而存活率或心率没有降低。TCS还降低ATP相关的呼吸和备用呼吸能力,并增加质子泄漏:线粒体解偶联的所有指标。我们的数据表明,TCS在体内是一种线粒体解偶联剂,在评估TCS的毒性和/或药物用途时应考虑到这一点。这是使用Seahorse细胞外通量分析仪以96孔测定格式测量每孔单个斑马鱼胚胎的生物能通量的第一个实例。在这项研究中开发的方法提供了一个高通量的工具,以确定以前未知的线粒体解偶联剂在活的生物体。
Triclosan (TCS) is a synthetic antimicrobial agent used in many consumer goods at millimolar concentrations. As a result of exposure, TCS has been detected widely in humans. We have recently discovered that TCS is a proton ionophore mitochondrial uncoupler in multiple types of living cells. Here we present novel data indicating that TCS is also a mitochondrial uncoupler in a living organism: 24 hour post fertilization zebrafish embryos. These experiments were conducted using a Seahorse Bioscience XFe 96 Extracellular Flux Analyzer modified for bidirectional temperature control, using the XF96 spheroid plate to position and measure one zebrafish embryo per well. Using this method, following acute exposure to TCS, basal oxygen consumption rate (OCR) increases, without a decrease in survival or heartbeat rate. TCS also decreases ATP-linked respiration and spare respiratory capacity and increases proton leak: all indicators of mitochondrial uncoupling. Our data indicate, that TCS is a mitochondrial uncoupler in vivo, which should be taken into consideration when assessing the toxicity and/or pharmaceutical uses of TCS. This is the first example of usage of a Seahorse Extracellular Flux Analyzer to measure bioenergetic flux of a single zebrafish embryo per well in a 96 well assay format. The method developed in this study provides a high-throughput tool to identify previously-unknown mitochondrial uncouplers in a living organism.
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