Gene Expression of Abcc2 and Its Regulation by Chicken Xenobiotic Receptor.
Gene Expression of Abcc2 and Its Regulation by Chicken Xenobiotic Receptor.
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DOI：
10.3390/toxics12010055
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发表时间：
2024-01-10
期刊：
影响因子：
4.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Gao Y;Deng H;Zhao Y;Li M;Wang L;Zhang Y
膜转运蛋白多药耐药相关蛋白2（MRP 2/Abcc 2）表现出很高的药理毒理学相关性，因为它输出多种细胞毒性化合物从细胞。然而，关于鸡MRP 2的基因表达和调控的详细信息尚未获得。本研究旨在研究Abcc 2在鸡不同组织中的表达分布，并确定Abcc 2的表达是否受鸡异生素受体（CXR）的诱导。生物信息学分析表明，MRP 2转运蛋白具有3个跨膜结构域（MSD）和2个高度保守的核苷酸结构域（NBD），与火鸡的进化关系密切。组织分布分析表明，Abcc 2在肝脏、肾脏、十二指肠和空肠中高度表达。当暴露于甲吡酮（CXR激动剂）和酮康唑（CXR拮抗剂）时，Abcc 2表达相应上调和下调。我们进一步证实了Abcc 2基因的调控依赖于CXR，分别通过过表达和干扰CXR。我们还证明了诱导Abcc 2表达和伊维菌素的活性，CXR是一个可能的调解人。动物实验表明，甲吡酮和伊维菌素诱导鸡的肝脏，肾脏和十二指肠的Abcc 2。总之，我们的研究确定了鸡Abcc 2的基因表达及其通过CXR的调控，这可能为合理使用兽药提供新的靶点。
Membrane transporter multidrug resistance-associated protein 2 (MRP2/Abcc2) exhibits high pharmaco-toxicological relevance because it exports multiple cytotoxic compounds from cells. However, no detailed information about the gene expression and regulation of MRP2 in chickens is yet available. Here, we sought to investigate the expression distribution of Abcc2 in different tissues of chicken and then determine whether Abcc2 expression is induced by chicken xenobiotic receptor (CXR). The bioinformatics analyses showed that MRP2 transporters have three transmembrane structural domains (MSDs) and two highly conserved nucleotide structural domains (NBDs), and a close evolutionary relationship with turkeys. Tissue distribution analysis indicated that Abcc2 was highly expressed in the liver, kidney, duodenum, and jejunum. When exposed to metyrapone (an agonist of CXR) and ketoconazole (an antagonist of CXR), Abcc2 expression was upregulated and downregulated correspondingly. We further confirmed that Abcc2 gene regulation is dependent on CXR, by overexpressing and interfering with CXR, respectively. We also demonstrated the induction of Abcc2 expression and the activity of ivermectin, with CXR being a likely mediator. Animal experiments demonstrated that metyrapone and ivermectin induced Abcc2 in the liver, kidney, and duodenum of chickens. Together, our study identified the gene expression of Abcc2 and its regulation by CXR in chickens, which may provide novel targets for the reasonable usage of veterinary drugs.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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DOI：
10.1016/j.jsbmb.2019.03.027
发表时间：
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