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斑马鱼作为研究 II 相胞质磺基转移酶的模型。

Zebrafish as a model for the study of the phase II cytosolic sulfotransferases.

机构信息

Department of Pharmacology, The University of Toledo, Toledo, OH 43606, USA.

出版信息

Curr Drug Metab. 2010 Jul;11(6):538-46. doi: 10.2174/138920010791636158.

Abstract

Cytosolic sulfotransferases (SULTs) are traditionally known as the Phase II drug-metabolizing or detoxifying enzymes that serve for the detoxification of drugs and other xenobiotics. These enzymes in general catalyze the transfer of a sulfonate group from the active sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), to low-molecular weight substrate compounds containing hydroxyl or amino group(s). Despite considerable efforts made in recent years, some fundamental aspects of the SULTs, particularly their ontogeny, cell type/tissue/organ-specific distribution, and physiological relevance, particularly their involvement in drug metabolism and detoxification, still remain poorly understood. To better understand these fundamental issues, we have embarked on developing the zebrafish as a model for studies concerning the SULTs. To date, fifteen zebrafish SULTs have been cloned, expressed, purified, and characterized. These zebrafish SULTs, which fall into four major SULT gene families, exhibited differential substrate specificities and distinct patterns of expression at different stages during embryogenesis, through larval development, and on to maturity. The information obtained, as summarized in this review, provides a foundation for further investigation into the physiological and pharmacological involvement of the SULTs using the zebrafish as a model.

摘要

细胞质磺基转移酶(SULTs)传统上被称为 II 相药物代谢或解毒酶,用于药物和其他外源性化合物的解毒。这些酶通常催化从活性硫酸盐 3'-磷酸腺苷 5'-磷酸硫酸酯(PAPS)向含有羟基或氨基的低分子量底物化合物转移磺酸盐基团。尽管近年来做出了相当大的努力,但 SULTs 的一些基本方面,特别是它们的个体发生、细胞类型/组织/器官特异性分布和生理相关性,特别是它们在药物代谢和解毒中的参与,仍然知之甚少。为了更好地理解这些基本问题,我们着手开发斑马鱼作为研究 SULTs 的模型。迄今为止,已经克隆、表达、纯化和表征了 15 种斑马鱼 SULTs。这些斑马鱼 SULTs 分为四个主要的 SULT 基因家族,在胚胎发生、幼虫发育和成熟过程的不同阶段表现出不同的底物特异性和不同的表达模式。本综述总结了所获得的信息,为进一步研究斑马鱼作为模型的 SULTs 的生理和药理学参与提供了基础。

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