脂筏参与耐药: 多药耐药相关ABC转运蛋白与脂筏的关系

脂筏(lipid raft)和细胞的许多功能,如信号转导、蛋白质和脂类的转运等都相关。近来有研究发现,与多药耐药密切相关的ABC转运蛋白(ATP-binding cassette transporter)定位于脂筏中,因此推测脂筏可能与耐药性有一定关系。本文综述了3种和耐药相关的ABC转运蛋白的定位与其功能之间的联系,分别是和肿瘤细胞多药耐药相关的ABC转运蛋白Pgp/ABCB1、MRP1/ABCC1以及与白假丝酵母菌(白念珠菌)多药耐药相关的ABC转运蛋白Cdr1p;并进一步讨论了脂筏的重要组成成分胆固醇和鞘脂对上述3种ABC转运蛋白的定位和功能的影响。

Lipid raft involved in drug resistance:relationship between multidrug resistance ATP-binding cassette transporters and lipid raft

Lipid rafts have been implicated in many cellular functions, including protein and lipid transport and signal transduction.ATP-binding cassette (ABC) transporters have also been localized in these membrane domains. Lipid rafts may have a certain relationship with drug resistance. In this review the evidence for this specific localization will be evaluated and discussed in terms of relevance to ABC transporter function. We will focus on three ABC transporters . Two of these transporters are relevant to multidrug resistance in tumor cells(Pgp/ABCB1 and MRP1/ABCC1),while the third (Cdr1) is relevant to multidrug resistance in candida albicans. In the context of lipid rafts, modulation of ABC transporter localization and function by two relevant lipid classes, sphingolipids and cholesterol will be discussed.