Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.
Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.
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DOI：
10.3389/fmicb.2015.00948
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发表时间：
2015
影响因子：
5.2
通讯作者：
Nair M
中科院分区：
文献类型：
--
作者：
Roy U;Barber P;Tse-Dinh YC;Batrakova EV;Mondal D;Nair M
多药耐药蛋白(MRPs)是三磷酸腺苷结合盒(ABC)药物外排转运蛋白超家族的成员。众所周知，MRP可调节高效抗逆转录病毒疗法(HAART)中使用的一系列抗逆转录病毒药物(ARV)和结核杆菌(TB)治疗中使用的抗菌剂的疗效。由于它们在谷胱甘肽(GSH)结合药物外流中的作用，MRP还可以调节细胞的氧化应激，这可能是HIV和/或TB发病的原因之一。本文综述了人类免疫缺陷病毒(HIV)感染细胞中受抗逆转录病毒药物影响的MRP家族成员的特征、功能表达和调控，并讨论了它们在HIV/TB所致功能障碍药物失效中的已知作用。目前，已鉴定出9个MRP家族成员(MRP1-MRP9)，其中MRP1和MRP2是研究最广泛的。这个家族其他成员的细节直到最近才被知道，但在炎症组织中的差异表达已经被记录下来。研究人员发现，MRP家族成员的分布、功能和反应性在不同类型的淋巴细胞和巨噬细胞中不同，并且在内皮细胞和上皮细胞的基底面和顶面都有差异表达。因此，这篇综述的主要目的是描述MRP转运体在HAART和TB治疗中的作用以及它们在这些慢性感染性疾病中表现出的细胞功能障碍的潜力。我们还概述了不同的可用选择和新的实验策略，这些策略正被用来克服这些膜转运蛋白介导的耐药性和疾病发病机制。
Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.