Sarkadi Balázs, Homolya László, Szakács Gergely, Váradi András
National Medical Center, Institute of Hematology and Immunology, Membrane Research Group, Budapest, Hungary.
Physiol Rev. 2006 Oct;86(4):1179-236. doi: 10.1152/physrev.00037.2005.
In this review we give an overview of the physiological functions of a group of ATP binding cassette (ABC) transporter proteins, which were discovered, and still referred to, as multidrug resistance (MDR) transporters. Although they indeed play an important role in cancer drug resistance, their major physiological function is to provide general protection against hydrophobic xenobiotics. With a highly conserved structure, membrane topology, and mechanism of action, these essential transporters are preserved throughout all living systems, from bacteria to human. We describe the general structural and mechanistic features of the human MDR-ABC transporters and introduce some of the basic methods that can be applied for the analysis of their expression, function, regulation, and modulation. We treat in detail the biochemistry, cell biology, and physiology of the ABCB1 (MDR1/P-glycoprotein) and the ABCG2 (MXR/BCRP) proteins and describe emerging information related to additional ABCB- and ABCG-type transporters with a potential role in drug and xenobiotic resistance. Throughout this review we demonstrate and emphasize the general network characteristics of the MDR-ABC transporters, functioning at the cellular and physiological tissue barriers. In addition, we suggest that multidrug transporters are essential parts of an innate defense system, the "chemoimmunity" network, which has a number of features reminiscent of classical immunology.
在本综述中，我们概述了一组ATP结合盒（ABC）转运蛋白的生理功能，这些蛋白最初被发现并至今仍被称为多药耐药（MDR）转运蛋白。尽管它们确实在癌症耐药中发挥重要作用，但其主要生理功能是提供针对疏水性外源性物质的普遍保护。这些必需的转运蛋白具有高度保守的结构、膜拓扑结构和作用机制，在从细菌到人类的所有生命系统中均有保留。我们描述了人类MDR-ABC转运蛋白的一般结构和机制特征，并介绍了一些可用于分析其表达、功能、调控和调节的基本方法。我们详细探讨了ABCB1（MDR1/P-糖蛋白）和ABCG2（MXR/BCRP）蛋白的生物化学、细胞生物学和生理学，并描述了与其他可能在药物和外源性物质耐药中起作用的ABCB型和ABCG型转运蛋白相关的新信息。在整个综述中，我们展示并强调了MDR-ABC转运蛋白在细胞和生理组织屏障中发挥作用的一般网络特征。此外，我们认为多药转运蛋白是固有防御系统“化学免疫”网络的重要组成部分，该网络具有许多类似于经典免疫学的特征。
