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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Upregulation of the heteromeric y +LAT2 transporter contributes to ammonia-induced increase of arginine uptake in rat cerebral cortical astrocytes
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Upregulation of the heteromeric y +LAT2 transporter contributes to ammonia-induced increase of arginine uptake in rat cerebral cortical astrocytes

机译：异聚y + LAT2转运蛋白的上调有助于氨诱导大鼠脑皮质星形胶质细胞摄取精氨酸。

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摘要

Increased l-Arg (Arg) uptake to astrocytes and neurons is thought to contribute to enhanced nitric oxide (NO) synthesis and oxidativeitrosative stress associated with hyperammonemia (HA). Recently we had shown that HA increases the expression in the brain of y +LAT2, an isoform of the y +L heteromeric transporter which promotes [ 3H]Arg efflux form brain cells in the presence of l-glutamine (Gln) (Zielińska et al.; 2011). In this study, we demonstrate that a significant proportion of [ 3H]Arg uptake to cultured cortical astrocytes is likewise mediated by system y +L, in addition to the uptake showing characteristics of systems y +, B 0+ and b 0+. However, stimulation of [ 3H]Arg uptake by treatment with 5 mM ammonium chloride ("ammonia") for 48 h could be solely ascribed to the y +L-mediated component of the uptake. Ammonia treatment increased the expression of the brain specific y +L isoform, y +LAT2, both at the mRNA and protein level, and silencing of the Slc7a6 gene coding for y +LAT2 protein specifically reduced the ammonia-induced [ 3H]Arg uptake. This study suggests an important role of y +LAT2 in the modulation of NO synthesis in the ammonia-exposed astrocytes.
机译：星形胶质细胞和神经元对l-Arg（Arg）的摄取增加被认为有助于一氧化氮（NO）的合成增强以及与高氨血症（HA）相关的氧化/亚硝化应激。最近，我们发现HA可以增加y + LAT2在大脑中的表达，y + LT2是γ+ L异源转运蛋白的同种型，在存在谷氨酰胺（Gln）的情况下，它会促进脑细胞的[3H] Arg外排（Zielińska等。; 2011）。在这项研究中，我们证明，除了显示系统y +，B 0+和b 0+的特征外，培养的皮质星形胶质细胞摄取[3H] Arg的比例也同样由系统y + L介导。但是，通过用5 mM氯化铵（“氨水”）处理48小时来刺激[3 H] Arg摄取可能完全归因于y + L介导的摄取。氨水处理可在mRNA和蛋白质水平上增加大脑特异性y + L亚型y + LAT2的表达，而沉默编码y + LAT2蛋白的Slc7a6基因的表达则特异性地降低了氨水诱导的[3H] Arg摄取。这项研究表明y + LAT2在暴露于氨的星形胶质细胞中NO合成的调节中的重要作用。

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