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在小鼠脑内有机溶质载体伴侣 1 的神经元表达、胞质定位和发育调控。

Neuronal expression, cytosolic localization, and developmental regulation of the organic solute carrier partner 1 in the mouse brain.

机构信息

Toxicology Laboratory, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, Kanagawa, 230-0074, Japan.

出版信息

Histochem Cell Biol. 2011 Mar;135(3):229-38. doi: 10.1007/s00418-011-0790-6. Epub 2011 Feb 18.

DOI:10.1007/s00418-011-0790-6
PMID:21331566
Abstract

Organic solute carrier partner 1 (OSCP1) is a mammalian, transporter-related protein that is able to facilitate the uptake of structurally diverse organic compounds into the cell when expressed in Xenopus laevis oocytes. This protein has been implicated in testicular handling of organic solutes because its mRNA expression is almost exclusive in the testis. However, in this study, we demonstrated significant expression of OSCP1 protein in mouse brain, the level of which was rather higher than that in the testis, although the corresponding mRNA expression was one-tenth of the testicular level. Immunohistochemistry revealed that OSCP1 was broadly distributed throughout the brain, and various neuronal cells were immunostained, including pyramidal cells in the cerebral cortex and hippocampus. However, there was no evidence of OSCP1 expression in glia. In primary cultures of cerebral cortical neurons, double-labeling immunofluorescence localized OSCP1 to the cytosol throughout the cell body and neurites including peri-synaptic regions. This was consistent with the subcellular fractionation of brain homogenates, in which OSCP1 was mainly recovered after centrifugation both in the cytosolic fraction and the particulate fraction containing synaptosomes. Immunoelectron microscopy of brain sections also demonstrated OSCP1 in the cytosol near synapses. In addition, it was revealed that changes in the expression level of OSCP1 correlated with neuronal maturation during postnatal development of mouse brain. These results indicate that OSCP1 may have a role in the brain indirectly mediating substrate uptake into the neurons in adult animals.

摘要

有机溶质载体伴侣 1(OSCP1)是一种哺乳动物转运蛋白相关的蛋白质,当在非洲爪蟾卵母细胞中表达时,它能够促进结构多样的有机化合物进入细胞。该蛋白质与睾丸对有机溶质的处理有关,因为其 mRNA 表达几乎只在睾丸中。然而,在这项研究中,我们证明了 OSCP1 蛋白在小鼠大脑中有显著表达,其水平虽然比睾丸低十分之一,但相当高。免疫组织化学显示 OSCP1 在大脑中广泛分布,各种神经元细胞被免疫染色,包括大脑皮层和海马体的锥体细胞。然而,在神经胶质细胞中没有 OSCP1 表达的证据。在大脑皮质神经元的原代培养中,双重标记免疫荧光将 OSCP1 定位在整个细胞体和神经突包括突触周围区域的细胞质中。这与大脑匀浆的亚细胞分级分离一致,其中 OSCP1 主要在细胞质部分和含有突触体的颗粒部分离心后回收。脑切片的免疫电子显微镜也证明了突触附近细胞质中的 OSCP1。此外,还揭示了 OSCP1 的表达水平变化与小鼠大脑出生后发育过程中的神经元成熟有关。这些结果表明,OSCP1 可能在大脑中具有间接作用,通过调节成年动物神经元的底物摄取来发挥作用。

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