Abstract：
Taurine, a sulfur-containing β-amino acid, is present at high concentrations in mammalian tissues and plays an important role in several essential biological processes. However, the genetic mechanisms involved in these physiological processes associated with taurine remain unclear. In this study, we investigated the regulatory mechanism underlying the taurine-induced transcriptional enhancement of the thioredoxin-interacting protein (TXNIP). The results showed that taurine significantly increased the luciferase activity of the human TXNIP promoter. Further, deletion analysis of the TXNIP promoter showed that taurine induced luciferase activity only in the TXNIP promoter region (+200 to +218). Furthermore, by employing a bioinformatic analysis using the TRANSFAC database, we focused on Tst-1 and Ets-1 as candidates involved in taurine-induced transcription and found that the mutation in the Ets-1 sequence did not enhance transcriptional activity by taurine. Additionally, chromatin immunoprecipitation assays indicated that the binding of Ets-1 to the TXNIP promoter region was enhanced by taurine. Taurine also increased the levels of phosphorylated Ets-1, indicating activation of Ets-1 pathway by taurine. Moreover, an ERK cascade inhibitor significantly suppressed the taurine-induced increase in TXNIP mRNA levels and transcriptional enhancement of TXNIP. These results suggest that taurine enhances TXNIP expression by activating transcription factor Ets-1 via the ERK cascade.
摘要：
牛磺酸,含硫的β-氨基酸,在哺乳动物组织中以高浓度存在，并在几个基本的生物学过程中起着重要作用。然而,与牛磺酸相关的这些生理过程中涉及的遗传机制仍不清楚。在这项研究中,我们研究了牛磺酸诱导的硫氧还蛋白相互作用蛋白（TXNIP）转录增强的调节机制。结果表明，牛磺酸显著提高了人TXNIP启动子的荧光素酶活性。Further,TXNIP启动子的缺失分析表明牛磺酸仅在TXNIP启动子区域（200至218）中诱导荧光素酶活性。此外，通过使用TRANSFAC数据库进行生物信息学分析，我们将Tst-1和Ets-1作为参与牛磺酸诱导转录的候选物,发现Ets-1序列中的突变并没有增强牛磺酸的转录活性.此外,染色质免疫沉淀测定表明牛磺酸增强了Ets-1与TXNIP启动子区的结合。牛磺酸还增加磷酸化Ets-1的水平,表明牛磺酸激活Ets-1途径。此外，ERK级联抑制剂可显着抑制牛磺酸诱导的TXNIPmRNA水平增加和TXNIP转录增强。这些结果表明牛磺酸通过ERK级联激活转录因子Ets-1来增强TXNIP表达。
