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ATP结合盒转运蛋白A6样亚组在小鼠脑实质和微血管中的基因表达。

Gene expression of A6-like subgroup of ATP-binding cassette transporters in mouse brain parenchyma and microvessels.

作者信息

Tachikawa Masanori, Toki Hidetoh, Watanabe Masahiko, Tomi Masatoshi, Hosoya Ken-Ichi, Terasaki Tetsuya

机构信息

Membrane Transport and Drug Targeting Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki, Aoba, Sendai, 980-8578, Japan.

Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

出版信息

Anat Sci Int. 2018 Sep;93(4):456-463. doi: 10.1007/s12565-018-0435-0. Epub 2018 Mar 8.

Abstract

The A-subclass of ATP-binding cassette (ABC) transporters is a highly conserved superfamily of potent lipid transporters. Although the ABCA1-like subgroup of ABCA1-4, and A7 have been shown to mediate the transport of endogenous lipids, the roles of the ABCA6-like subgroup transporters, which have been identified as a unique gene cluster on human chromosome 17q24 (ABCA5, A6, A8, A9, and A10) and mouse chromosome 11 (Abca5, a6, a8a, a8b, and a9), remains largely unknown. The purpose of the present study was to clarify the spatial and temporal expression profiles of Abca6-like subgroup transporters in embryonic and postnatal mouse brains by a combination of in situ hybridization and quantitative polymerase chain reaction (PCR) using magnetically isolated brain vascular endothelial cells. In embryonic brains, the transcripts of Abca5, a8a and a8b were detected predominantly in the mantle zone, where postmitotic neurons differentiate. At the postnatal stages, they were expressed in various nuclei and neuronal layers. Abca9 mRNA was detected diffusely in the embryonic and postnatal brains and sequential and/or strong spotted signals were detected in the leptomeninges on the brain surface. PCR detected expression of Abca8a and Abca9 mRNAs in isolated vascular endothelial cells. Expression signals for Abca6 mRNA were hardly observed at any stages examined. These distinct spatio-temporal expression patterns of Abca6-like subgroup transporters may reflect their functional significance and diversity to regulate lipid transport, particularly in neurons, leptomeningeal cells, and vascular endothelial cells.

摘要

ATP结合盒(ABC)转运蛋白的A亚类是一类高度保守的强效脂质转运蛋白超家族。尽管已证明ABCA1 - 4以及A7的ABCA1样亚组可介导内源性脂质的转运,但ABCA6样亚组转运蛋白的作用仍 largely未知,该亚组转运蛋白已被确定为人类染色体17q24(ABCA5、A6、A8、A9和A10)和小鼠染色体11(Abca5、a6、a8a、a8b和a9)上的一个独特基因簇。本研究的目的是通过原位杂交和定量聚合酶链反应(PCR)相结合的方法,使用磁分离的脑血管内皮细胞,阐明Abca6样亚组转运蛋白在胚胎期和出生后小鼠大脑中的时空表达谱。在胚胎大脑中,Abca5、a8a和a8b的转录本主要在有丝分裂后神经元分化的套层区域被检测到。在出生后阶段,它们在各种核团和神经元层中表达。Abca9 mRNA在胚胎期和出生后大脑中均有弥漫性表达,并且在脑表面的软脑膜中检测到连续和/或强烈的斑点信号。PCR检测到Abca8a和Abca9 mRNA在分离的血管内皮细胞中的表达。在任何检测阶段几乎都未观察到Abca6 mRNA的表达信号。Abca6样亚组转运蛋白这些独特的时空表达模式可能反映了它们在调节脂质转运方面的功能意义和多样性,特别是在神经元、软脑膜细胞和血管内皮细胞中。

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