Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Biochem Biophys Res Commun. 2012 Sep 28;426(3):433-7. doi: 10.1016/j.bbrc.2012.08.116. Epub 2012 Aug 30.
Taurine (2-aminoethanesulfonic acid), a sulfur-containing β-amino acid, plays an important role in several essential biological processes; although, the underlying mechanisms for these regulatory functions remain to be elucidated, especially at the genetic level. We investigated the effects of taurine on the gene expression profile in Caco-2 cells using DNA microarray. Taurine increased the mRNA expression of thioredoxin interacting protein (TXNIP), which is involved in various metabolisms and diseases. β-Alanine or γ-aminobutyric acid (GABA), which are structurally or functionally related to taurine, did not increase TXNIP mRNA expression. These suggest the expression of TXNIP mRNA is induced specifically by taurine. β-Alanine is also known to be a substrate of taurine transporter (TAUT) and competitively inhibits taurine uptake. Inhibition of taurine uptake by β-alanine eliminated the up-regulation of TXNIP, which suggests TAUT is involved in inducing TXNIP mRNA expression. The up-regulation of TXNIP mRNA expression by taurine was also observed at the protein level. Furthermore, taurine significantly increased TXNIP promoter activity. Our present study demonstrated the taurine-specific phenomenon of TXNIP up-regulation, which sheds light on the physiological function of taurine.
牛磺酸(2-氨基乙磺酸)是一种含硫的β-氨基酸,在几种重要的生物过程中发挥重要作用;尽管这些调节功能的潜在机制仍有待阐明,特别是在遗传水平上。我们使用 DNA 微阵列研究了牛磺酸对 Caco-2 细胞基因表达谱的影响。牛磺酸增加了与各种代谢和疾病相关的硫氧还蛋白相互作用蛋白(TXNIP)的 mRNA 表达。与牛磺酸在结构或功能上相关的β-丙氨酸或γ-氨基丁酸(GABA)没有增加 TXNIP mRNA 的表达。这表明 TXNIP mRNA 的表达是由牛磺酸特异性诱导的。β-丙氨酸也是牛磺酸转运体(TAUT)的底物,竞争性抑制牛磺酸摄取。β-丙氨酸抑制牛磺酸摄取消除了 TXNIP 的上调,这表明 TAUT 参与诱导 TXNIP mRNA 的表达。牛磺酸还能在蛋白水平上调 TXNIP mRNA 的表达。此外,牛磺酸显著增加了 TXNIP 启动子活性。本研究表明了牛磺酸特异性上调 TXNIP 的现象,这为牛磺酸的生理功能提供了线索。