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牛磺酸诱导硫氧还蛋白相互作用蛋白（TXNIP）上调的信号通路

Signaling Pathway of Taurine-Induced Upregulation of TXNIP.

作者信息

Satsu Hideo, Gondo Yusuke, Shimanaka Hana, Imae Masato, Murakami Shigeru, Watari Kenji, Wakabayashi Shunichi, Park Sung-Joon, Nakai Kenta, Shimizu Makoto

机构信息

Department of Biotechnology, Faculty of Engineering, Maebashi Institute of Technology, Gunma 371-0816, Japan.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.

出版信息

Metabolites. 2022 Jul 11;12(7):636. doi: 10.3390/metabo12070636.

DOI:10.3390/metabo12070636
PMID:35888758
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9317136/
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

牛磺酸是一种含硫的β-氨基酸，在哺乳动物组织中含量很高，并在多个重要生物过程中发挥重要作用。然而，与牛磺酸相关的这些生理过程所涉及的遗传机制仍不清楚。在本研究中，我们调查了牛磺酸诱导硫氧还蛋白相互作用蛋白（TXNIP）转录增强的调控机制。结果表明，牛磺酸显著增加了人TXNIP启动子的荧光素酶活性。此外，对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）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因子，并发现Ets-1序列中的突变不会增强牛磺酸的转录活性。此外，染色质免疫沉淀分析表明，牛磺酸增强了Ets-1与TXNIP启动子区域的结合。牛磺酸还增加了磷酸化Ets-1的水平，表明牛磺酸激活了Ets-1通路。此外，一种ERK级联抑制剂显著抑制了牛磺酸诱导的TXNIP mRNA水平的增加和TXNIP的转录增强。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的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/5a6709b0bacc/metabolites-12-00636-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/c8b51336afa7/metabolites-12-00636-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/802b63625490/metabolites-12-00636-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/5a6709b0bacc/metabolites-12-00636-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/7f4606838ddf/metabolites-12-00636-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/3c5bf0e98fab/metabolites-12-00636-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/872129b54d9f/metabolites-12-00636-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/792667e82878/metabolites-12-00636-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/c8b51336afa7/metabolites-12-00636-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/3bc82ecb0265/metabolites-12-00636-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/bdb876bda883/metabolites-12-00636-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/802b63625490/metabolites-12-00636-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/8a896bbc880a/metabolites-12-00636-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/e4e26730fdcd/metabolites-12-00636-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/94eecce5f4ae/metabolites-12-00636-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/9317136/5a6709b0bacc/metabolites-12-00636-g011.jpg

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Functions of Maternally-Derived Taurine in Fetal and Neonatal Brain Development.牛磺酸在胎儿和新生儿大脑发育中的作用。
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