Expression and immunolocalization of the multidrug resistance proteins, Mrp1-Mrp6 (ABCC1-ABCC6), in human brain
Expression and immunolocalization of the multidrug resistance proteins, Mrp1-Mrp6 (ABCC1-ABCC6), in human brain
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DOI：
10.1016/j.neuroscience.2004.07.051
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Keppler, D
中科院分区：
文献类型：
--
作者：
Nies, AT;Jedlitschky, G;Keppler, D
多药耐药蛋白（MRP，符号ABCC）是介导ATP依赖性的有机阴离子（包括细胞毒性和抗病毒药物）从细胞中输出的膜糖蛋白。为了确定MRP家族成员可能参与人脑对细胞毒性和抗病毒药物的内在抗性，我们分析了MRP 1-MRP 6在神经外科手术期间获得的几个成人大脑区域的快速冷冻病灶周围样本中的表达和定位。定量聚合酶链反应分析显示MRP 1、MRP 2、MRP 3、MRP 4和MRP 5 mRNA表达，而MRP 6 mRNA低于可检测性。然而，人脑冷冻切片的免疫荧光显微镜显示对MRP 2或MRP 3蛋白没有反应性。蛋白质MRP 1，MRP 4，和MRP 5的共聚焦激光扫描显微镜清楚地定位到脑毛细血管内皮细胞的腔侧。在皮质下白色物质的星形胶质细胞中也检测到MRP 4和MRP 5蛋白。值得注意的是，MRP 5蛋白存在于锥体神经元中。因此，MRP蛋白可能有助于内源性阴离子谷胱甘肽或葡萄糖醛酸结合物（MRP 1的底物）、环核苷酸（MRP 4和MRP 5的底物）或谷胱甘肽（MRP 1和MRP 4的共底物）的细胞外排;此外，它们可能在脑对几种细胞毒性和抗病毒药物的抗性中发挥重要作用。(C)2004年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Multidrug resistance proteins (MRPs, symbol ABCC) are membrane glycoproteins that mediate the ATP-dependent export of organic anions, including cytotoxic and antiviral drugs, from cells. To identify MRP family members possibly involved in the intrinsic resistance of human brain to cytotoxic and antiviral drugs, we analyzed the expression and localization of MRP1-MRP6 in rapidly frozen perilesional samples of several regions of adult human brain obtained during neurosurgery. Quantitative polymerase chain reaction analysis showed expression of MRP1, MRP2, MRP3, MRP4, and MRP5 mRNA, whereas MRP6 mRNA was below detectability. However, immunofluorescence microscopy of cryosections from human brain showed no reactivity for the MRP2 or MRP3 proteins. The proteins MRP1, MRP4, and MRP5 were clearly localized by confocal laser scanning microscopy to the luminal side of brain capillary endothelial cells. The MRP4 and MRP5 proteins were also detected in astrocytes of the subcortical white matter. Notably, MRP5 protein was present in pyramidal neurons. MRP proteins may, thus, contribute to the cellular efflux of endogenous anionic glutathione or glucuronate conjugates (substrates for MRP1), cyclic nucleotides (substrates for MRP4 and MRP5), or glutathione (co-substrate for MRP1 and MRP4); in addition, they may play an important role in the resistance of the brain to several cytotoxic and antiviral drugs. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.