Signaling Pathway of Taurine-Induced Upregulation of TXNIP.

Taurine, a sulfur-containing ß-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.

Effect of Taurine on Cell Function via TXNIP Induction in Caco-2 Cells.

Taurine (2-aminoethanesulfonic acid), a sulfur-containing ß-amino acid, is a free amino acid present in high concentrations in mammalian tissues. Taurine has pivotal roles in anti-oxidation, membrane stabilization, osmoregulation, anti-inflammation, and other process. In a DNA microarray analysis, we previously found that taurine markedly increases the mRNA expression of thioredoxin interacting protein (TXNIP) in Caco-2 cells. In this study, we investigated the effect of these taurine-induced changes in TXNIP on the function of Caco-2 cells. We found that taurine decreases glucose uptake in a dose-dependent manner. The taurine-induced decrease in glucose uptake was completely abolished by transfection with siRNA against TXNIP, suggesting that TXNIP is involved in the taurine-induced down-regulation of glucose uptake. We also revealed that taurine induces AMPK activation and further increases the intracellular ATP content in Caco-2 cells. These results suggest that taurine could regulate the function of Caco-2 cells via TXNIP induction, leading to extend our understanding of the functions of taurine.