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小鼠脑内胶质母细胞瘤的发展:有机阳离子转运体(OCTs)普遍减少,OCT3转运体定位错误,随后天冬氨酸(ASP)底物被摄取到细胞核中。

Glioblastoma development in mouse brain: general reduction of OCTs and mislocalization of OCT3 transporter and subsequent uptake of ASP substrate to the nuclei.

作者信息

Kucheryavykh Lilia Y, Rolón-Reyes Kimberleve, Kucheryavykh Yuriy V, Skatchkov Serguei, Eaton Misty J, Sanabria Priscila, Wessinger William D, Inyushin Mikhail

机构信息

Dept. of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00960, USA.

Dept. of Biochemistry and Physiology, Universidad Central del Caribe, Bayamon, PR 00960, USA.

出版信息

J Neurosci Neuroeng. 2014 Feb;3(1):3-9. doi: 10.1166/jnsne.2014.1091.

Abstract

Organic cation transporters (OCTs) were first found and then isolated from cultured glioma cells. When glioma cells are implanted into brain the fate of OCTs varies with time after implantation and transporter type. Here we report that OCT1, OCT2 and OCT3 immunofluorescence is significantly reduced over time in implanted GL261 glioma cells, during tumor development in the brain. By day 21 after glioma implantation, OCT1, OCT2 and OCT3 immunofluorescence was reduced more than 10-fold in the cytoplasm of glioma cells, while OCT3 immunofluorescence became concentrated in the nucleus. The well-known fluorescent substrate for OCT transporters, 4-(4-(dimethylamino)-styryl)-N-methylpyridinium iodide (ASP), previously shown to accumulate in glioma-cell cytoplasm in slices, began to accumulate in the nucleus of these cells, but not in cytoplasm, after 21 days post-implantation. Considering this mislocalization phenomenon, and other literature on similar nuclear mislocalization of different transporters, receptors and channels in glioma cells, we suggest that it is one of the "omens" preceding the motility and aggressivity changes in glioma behavior.

摘要

有机阳离子转运体(OCTs)最初是在培养的胶质瘤细胞中被发现并分离出来的。当胶质瘤细胞植入大脑后,OCTs的命运会随着植入后的时间以及转运体类型而变化。在此我们报告,在脑内肿瘤发展过程中,植入的GL261胶质瘤细胞中,OCT1、OCT2和OCT3的免疫荧光会随着时间显著降低。在胶质瘤植入后第21天,胶质瘤细胞胞质中的OCT1、OCT2和OCT3免疫荧光降低了10倍以上,而OCT3免疫荧光则集中在细胞核中。OCT转运体的著名荧光底物4-(4-(二甲氨基)-苯乙烯基)-N-甲基碘化吡啶(ASP),之前显示在切片中积聚于胶质瘤细胞胞质,在植入后21天开始积聚于这些细胞的细胞核而非胞质中。考虑到这种定位错误现象以及其他关于胶质瘤细胞中不同转运体、受体和通道类似核定位错误的文献,我们认为这是胶质瘤行为中运动性和侵袭性变化之前的“预兆”之一。

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