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ABC转运蛋白P-糖蛋白/Abcb1亚型和乳腺癌耐药蛋白/Abcg2在小鼠早期发育过程中的时空表达及外排活性

Temporal/spatial expression and efflux activity of ABC transporter, P-glycoprotein/Abcb1 isoforms and Bcrp/Abcg2 during early murine development.

作者信息

Sawicki Wojciech T, Kujawa Marek, Jankowska-Steifer Ewa, Mystkowska Ewa T, Hyc Anna, Kowalewski Cezary

机构信息

Department of Histology and Embryology, Medical University of Warsaw, Poland.

出版信息

Gene Expr Patterns. 2006 Oct;6(7):738-46. doi: 10.1016/j.modgep.2005.12.003. Epub 2006 Feb 2.

DOI:10.1016/j.modgep.2005.12.003
PMID:16458078
Abstract

ABC transporters pump out from cells a large number of endo- and xenobiotics including signal molecules and toxins; they are molecular markers of stem/progenitor cells as well. Here, we present the study of temporal/spatial patterns of Abcb1 isoforms and Abcg2 transporter expression and efflux activity in pre- and early postimplantation murine embryos. We found in 2-cell embryos abcb1a, abcb1b and abcg2 mRNAs which were believed to be maternally inherited. The expression of abcb1b and abcg2 genes was found in blastocysts and in 7 days postcoitum (dpc) embryos, while in 9dpc embryos beside of abcb1b/abcg2, the abcb1a gene was expressed. The abcb2 mRNA was detectable neither in pre- nor in postimplantation embryos. Moreover, we analysed temporal/spatial patterns of rhodamine 123/Hoechst 33342 efflux, which mirrors the ABC transporter phenotype, from individual cells of pre- and postimplantation murine embryos. The blastomeres of 2-, 4- and 8-cell embryos had efflux-inactive phenotype. Single, efflux-active cells emerged first in the morulae and their number increased in blastocyst inner cell mass. In 6 and 7 dpc embryos, all embryonic cells hold the efflux-active phenotype. Proximal embryonic endoderm of 6-8 dpc embryos contained two sub-domains: one consisted of efflux-active cells and another one of efflux-inactive cells reflecting polarity of an embryo. Between 7 and 8 dpc, at the onset of organogenesis, the vehement surge of efflux-inactive embryonic cells occurred, and their number increased in 9 dpc embryos, which consequently contained few efflux-active cells.

摘要

ABC转运蛋白可将包括信号分子和毒素在内的大量内源性和外源性物质泵出细胞;它们也是干/祖细胞的分子标志物。在此,我们展示了对植入前和植入后早期小鼠胚胎中Abcb1亚型和Abcg2转运蛋白表达及外排活性的时空模式的研究。我们在2细胞胚胎中发现了abcb1a、abcb1b和abcg2 mRNA,据信它们是母系遗传的。在囊胚和妊娠7天(dpc)的胚胎中发现了abcb1b和abcg2基因的表达,而在9dpc胚胎中,除了abcb1b/abcg2外,abcb1a基因也有表达。在植入前和植入后的胚胎中均未检测到abcb2 mRNA。此外,我们分析了罗丹明123/ Hoechst 33342外排的时空模式,其反映了ABC转运蛋白表型,来自植入前和植入后小鼠胚胎的单个细胞。2细胞、4细胞和8细胞胚胎的卵裂球具有外排无活性表型。单个外排活性细胞首先出现在桑葚胚中,其数量在囊胚内细胞团中增加。在6和7 dpc胚胎中,所有胚胎细胞都具有外排活性表型。6 - 8 dpc胚胎的近端胚胎内胚层包含两个亚域:一个由外排活性细胞组成,另一个由外排无活性细胞组成,反映了胚胎的极性。在7至8 dpc之间,在器官发生开始时,外排无活性胚胎细胞急剧增加,其数量在9 dpc胚胎中增加,因此9 dpc胚胎中含有少量外排活性细胞。

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