Regulation of gene expression by D-amino acids

D-氨基酸对基因表达的调节

• 批准号: 13672296
• 负责人: HOMMA Hiroshi
• 金额: $ 2.3万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672296/
• 关键词: D-Aspartate; testosterone; Steroidogenic acute regulatory protein; Leydig cells; steroidogenesis; glutamate transporter; mLTC-1 cells; Steroidogenic Acute Regulatory protein; ヒト絨毛性性腺刺激ホルモン; 8-Br-cAMP

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.

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。

项目成果

Long,Z., et al.: "Immunocytochemical study of D-aspartate in the 2068 rat pheochromocytoma cell line"Bioimages. 9. 61-67 (2001)

Long,Z., et al.：“2068 大鼠嗜铬细胞瘤细胞系中 D-天冬氨酸的免疫细胞化学研究”生物图像。

Long, Z.et al.: "D-Aspartate in a prolactin-secreting clonal strain of rat pituitary tumor cells (GH3)"Biochem. Biophys. Res. Commun.. 276. 1143-1147 (2000)

Long, Z. 等人：“大鼠垂体肿瘤细胞 (GH3) 的催乳素分泌克隆株中的 D-天冬氨酸”Biochem。

Long,Z., et al.: "Cell density inversely regulates D- and L-aspartate levels in rat pheochromocytoma MPT1 cells"Arch. Biochem. Biophys. 404. 92-97 (2002)

Long,Z. 等人：“细胞密度反向调节大鼠嗜铬细胞瘤 MPT1 细胞中的 D-和 L-天冬氨酸水平”Arch.

Long, Z. et al.: "Occurence of D-amino acids and a pyridoxal 5'-phosphate-dependent aspartate racemase in the acidothermophilic archeon, Thermoplasma acidophilum"Biochem.Biophys.Res.Commun.. 281. 317-321 (2001)

Long, Z. 等人：“嗜酸古菌、嗜酸热原体中 D-氨基酸和吡哆醛 5-磷酸依赖性天冬氨酸消旋酶的出现”Biochem.Biophys.Res.Commun. 281. 317-321 (2001

Long, Z.et al.: "Occurrence of D-amino acids and a pyridoxal 5'-phosphate-dependent aspartate racemase in the acidothermophilic archeon, Thermoplasma acidophilum"Biochem. Biophys. Res. Commun.. 281. 317-321 (2001)

Long, Z. 等人：“D-氨基酸和吡哆醛 5-磷酸依赖性天冬氨酸消旋酶在嗜酸嗜热古菌、嗜酸热原体中的出现”Biochem。