Regulation of gene expression by D-amino acids

我们已经报道，D-天冬氨酸（D-Asp）增加人绒毛膜促性腺激素（hCG）诱导的睾丸激素的生产在纯化的大鼠Laydig细胞。推测D-Asp被细胞摄取并增加类固醇生成急性调节蛋白（StAR）的蛋白和mRNA水平，StAR是类固醇生成的必需蛋白。我们在这项研究中发现，D-Asp增加了mLTC-1细胞（小鼠Leydig肿瘤细胞-1）中星星蛋白的表达，这是一种培养的细胞系，可以作为大鼠Leydig细胞的合适模型。在这些细胞中，只有当细胞瞬时表达谷氨酸转运蛋白时，D-Asp才促进星星蛋白的表达，D-Asp通过谷氨酸转运蛋白被吸收到细胞中。该结果表明，D-Asp摄取对于刺激星星基因表达是必需的。此外，D-Asp在稳定表达谷氨酸转运体的细胞中刺激星星蛋白的表达，而在亲本mLTC-1细胞中不促进蛋白的表达。这些证据表明，D-Asp应该在刺激星星基因表达之前被吸收到mLTC-1细胞中。应阐明D-Asp刺激mLTC-1细胞中星星基因表达的机制。

We have reported that D-aspartate (D-Asp) increases human chorionic gonadotropin (hCG)-induced testosterone production in purified rat Laydig cells. D-Asp is presumed to be taken up into the cells and increases the protein and mRNA levels of Steroidogenic acute regulatory protein (StAR), which is an essential protein for the steroidogenesis. We found in this study that D-Asp increases StAR protein expression in mLTC-1 cells (mouse Leydig Tumor Cell-1), a cultured cell line that would be a suitable model of rat Leydig cells. In these cells, D-Asp promotes StAR protein expression only when the cells transiently express glutamate transporter, through which D-Asp is taken up into the cells. This result shows that D-Asp uptake is necessary for the stimulation of StAR gene expression. In addition, D-Asp stimulates StAR protein expression in the cells which stably express glutamate transporter, while it did not promote the protein expression in the parent mLTC-1 cells. These lines of evidence show that D-Asp should be taken up into mLTC-1 cells before it stimulates StAR gene expression. Details should be clarified on the mechanism of D-Asp stimulation of StAR gene expression in mLTC-1 cells.