L-glutamate in the extracellular space regulates endogenous D-aspartate homeostasis in rat pheochromocytoma MPT1 cells
L-glutamate in the extracellular space regulates endogenous D-aspartate homeostasis in rat pheochromocytoma MPT1 cells
复制标题
DOI：
10.1016/j.abb.2004.01.016
复制
发表时间：
2004-04-01
影响因子：
3.9
通讯作者：
Homma, H
中科院分区：
文献类型：
--
作者：
Adachi, M;Koyama, H;Homma, H
在以前的研究中[FEBS Lett. 434（1998）231，Arch. Biochem. Biophys. 404（2002）92]，我们首次证明D-天冬氨酸（D-Asp）在培养的哺乳动物细胞系中合成，例如嗜铬细胞瘤12（PC 12）及其亚克隆MPTI。我们目前的重点是在这些细胞中的D-Asp稳态的动态分析。在这次交流中，我们表明，L-谷氨酸（Glu）和L-Glu转运底物在细胞外空间调节内源性D-Asp在MPT 1细胞的稳态。D-Asp显然处于动态稳态，内源性D-Asp通过一种不确定的机制不断释放到细胞外空间，并通过L-Glu转运蛋白持续而密集地摄入细胞。在这些条件下，培养基中的L-Glu及其转运蛋白底物可以竞争性地抑制D-Asp通过转运蛋白的摄取，导致氨基酸在细胞外空间中的积累。我们还证明，DL-TBOA，一个完善的L-Glu转运蛋白抑制剂，是由转运蛋白在很长的时间间隔，但不是在一个短的时间尺度。(C)2004年爱思唯尔公司All rights reserved.
In previous studies [FEBS Lett. 434 (1998) 231, Arch. Biochem. Biophys. 404 (2002) 92], we demonstrated for the first time that D-aspartate (D-Asp) is synthesized in cultured mammalian cell lines, such as pheochromocytorna 12 (PC12) and its subclone, MPTI. Our current focus is analysis of the dynamics of D-Asp homeostasis in these cells. In this communication, we show that L-glutamate (Glu) and L-Glu transporter substrates in the extracellular space regulate the homeostasis of endogenous D-Asp in MPT1 Cells. D-Asp is apparently in dynamic homeostasis, whereby endogenOUS D-Asp is constantly released into the extracellular space by an undefined mechanism, and continuously and intensively taken up into cells by an L-Glu transporter. Under these conditions, L-Glu and its transporter substrates in the medium may competitively inhibit the uptake Of D-Asp via the transporter, resulting in accumulation of the amino acid in the extracellular space. We additionally demonstrate that DL-TBOA, a well-established L-Glu transporter inhibitor, is taken up by the transporter during long time intervals, but not on a short time-scale. (C) 2004 Elsevier Inc. All rights reserved.