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多药外排泵P-糖蛋白在人类造血干细胞中的表达与活性

Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells.

作者信息

Chaudhary P M, Roninson I B

机构信息

Department of Genetics, University of Illinois, Chicago 60612.

出版信息

Cell. 1991 Jul 12;66(1):85-94. doi: 10.1016/0092-8674(91)90141-k.

DOI:10.1016/0092-8674(91)90141-k
PMID:1712673
Abstract

Hematopoietic stem cells show reduced staining with a mitochondrial fluorescent dye, rhodamine 123 (Rh-123), which was supposed to indicate decreased mitochondrial activity in these cells. Rh123 and several other fluorescent dyes are substrates for transport mediated by P-glycoprotein (P-gp), an efflux pump responsible for multidrug resistance in tumor cells. We have found that staining of human bone marrow cells with fluorescent dyes is potentiated by P-gp inhibitors and inversely correlated with P-gp expression. P-gp is expressed in practically all hematopoietic progenitor cells, including long-term culture-initiating cells. The highest levels of P-gp among the progenitors are associated with cells displaying characteristics of pluripotent stem cells. These results have implications for stem cell purification and bone marrow resistance to cancer chemotherapy.

摘要

造血干细胞用线粒体荧光染料罗丹明123(Rh-123)染色减少,这被认为表明这些细胞中线粒体活性降低。Rh123和其他几种荧光染料是由P-糖蛋白(P-gp)介导的转运底物,P-糖蛋白是一种负责肿瘤细胞多药耐药性的外排泵。我们发现,P-gp抑制剂可增强荧光染料对人骨髓细胞的染色,且与P-gp表达呈负相关。P-gp几乎在所有造血祖细胞中都有表达,包括长期培养起始细胞。祖细胞中P-gp水平最高的与具有多能干细胞特征的细胞相关。这些结果对干细胞纯化和骨髓对癌症化疗的抗性具有重要意义。

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