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药物转运体在人类多能干细胞及早期组织分化中的重要性。

The importance of drug transporters in human pluripotent stem cells and in early tissue differentiation.

作者信息

Apáti Ágota, Szebényi Kornélia, Erdei Zsuzsa, Várady György, Orbán Tamás I, Sarkadi Balázs

机构信息

a Institute of Enzymology , Research Centre for Natural Sciences , Budapest 1117 , Hungary.

出版信息

Expert Opin Drug Metab Toxicol. 2016;12(1):77-92. doi: 10.1517/17425255.2016.1121382. Epub 2015 Dec 14.

Abstract

INTRODUCTION

Drug transporters are large transmembrane proteins which catalyse the movement of a wide variety of chemicals, including drugs as well as xeno- and endobiotics through cellular membranes. The major groups of these proteins include the ATP-binding cassette transporters which in eukaryotes work as ATP-fuelled drug 'exporters' and the Solute Carrier transporters, with various transport directions and mechanisms.

AREAS COVERED

In this review, we discuss the key ATP-binding cassette and Solute Carrier drug transporters which have been reported to contribute to the function and/or protection of undifferentiated human stem cells and during tissue differentiation. We review the various techniques for studying transporter expression and function in stem cells, and the role of drug transporters in foetal and placental tissues is also discussed. We especially focus on the regulation of transporter expression by factors modulating cell differentiation properties and on the function of the transporters in adjustment to environmental challenges.

EXPERT OPINION

The relatively new and as yet unexplored territory of transporters in stem cell biology may rapidly expand and bring important new information regarding the metabolic and epigenetic regulation of 'stemness' and the early differentiation properties. Drug transporters are clearly important protective and regulatory components in stem cells and differentiation.

摘要

引言

药物转运蛋白是大型跨膜蛋白,可催化多种化学物质通过细胞膜移动,这些化学物质包括药物以及外源性和内源性生物活性物质。这些蛋白的主要类别包括ATP结合盒转运蛋白,在真核生物中,它作为由ATP供能的药物“输出器”发挥作用,以及溶质载体转运蛋白,具有多种转运方向和机制。

涵盖领域

在本综述中,我们讨论了关键的ATP结合盒和溶质载体药物转运蛋白,据报道这些转运蛋白有助于未分化的人类干细胞的功能和/或保护以及组织分化过程。我们回顾了研究干细胞中转运蛋白表达和功能的各种技术,还讨论了药物转运蛋白在胎儿和胎盘组织中的作用。我们特别关注调节细胞分化特性的因素对转运蛋白表达的调控以及转运蛋白在应对环境挑战中的功能。

专家观点

干细胞生物学中相对较新且尚未探索的转运蛋白领域可能会迅速扩展,并带来有关“干性”的代谢和表观遗传调控以及早期分化特性的重要新信息。药物转运蛋白显然是干细胞和分化过程中重要的保护和调节成分。

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