摘要
硫氧还蛋白相互作用蛋白(TXNIP)不仅与细胞的氧化还原状态密切相关,在胰岛β细胞功能障碍和细胞凋亡中也扮演了重要角色。高糖通过招募碳水化合物反应元件结合蛋白(ChREBP)到TXNIP的启动子,ChREBP与组蛋白乙酰转移酶p300相互作用,引起TXNIP的转录,TXNIP介导高糖诱发的氧化应激、内质网应激、NOD样受体3炎症小体激活、凋亡和自噬障碍等。可通过诱导微小RNA-204的表达下调鸟类Maf A蛋白哺乳动物同系物而抑制胰岛素基因转录,抑制胰岛素信号转导途径,进而抑制葡萄糖刺激的胰岛素分泌;TXNIP通过抑制硫氧还蛋白系统影响细胞的生存,同时还是介导细胞线粒体凋亡和内质网应激凋亡途径的枢纽分子。抑制TXNIP可能是一个阻止糖尿病进程的有效靶点。本文就TXNIP在胰岛细胞凋亡和胰岛功能障碍方面的相关研究进行回顾和总结分析。
Thioredoxin interaction protein （TXNIP） is closely related to the cell redox state and plays an important role in pancreatic islet IB cell apoptosis and dysfunction. High glucose recruits carbohydrate response element-binding protein （ChREBP） to the txnip promoter while ChREBP interacts with p300, inducing H4 acetylation. ChREBP is a transcription factor that mediates glucose-induced TXNIP expres- sion, TXNIP up-regulation leads to oxidative stress, ER stress/inflammation, NOD like receptor protein 3 activation, autophagic dysfunction and apoptosis. TXNIP induces microRNA-204 expression to down-reg- ulate MafA, leading to insulin transcription suppression. TXNIP inhibits both insulin signal transduction pathway and glucose stimulated insulin secretion. TXNIP affects cell survival by suppressing TRX system. TXNIP is the key molecule that mediates mitochondria and endoplasmic reticulum apoptosis. Researches about the role of TXNIP in apoptosis and dysfunction of pancreatic islet cells are reviewed in this article.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2015年第3期482-485,共4页
Chinese Journal of Pharmacology and Toxicology
基金
新疆维吾尔自治区自然科学基金(2012211A038)~~
