摘要
组织细胞可经过多种途径产生氧自由基(ROS),而肿瘤组织由于多种应激因素会产生大量ROS,其中最重要的是过氧化氢(H2O2).H2O2对细胞发挥着致损伤及亚毒性信使的双重作用,作为信使其不仅参与调节正常细胞信号通路,重要的是促进肿瘤的发生及进展.ROS作为一种应激刺激信号激活细胞内的AP-1(activator protein 1)、Nrf-2(NF-E2-related factor 2)等核转录因子,活化后的AP-1、Nrf-2会结合到硫氧还蛋白(sulfiredoxin,SRX)基因启动子上游的调控序列,促进SRX基因的表达.SRX的表达上调则影响其下游的抗氧化蛋白,即特定亚型的过氧化物氧还蛋白(peroxiredoxin,PRX)的活性状态,最终使细胞内H2O2浓度受到调节.由SRX-PRX轴与H2O2形成1个环路,通过调节H2O2含量来参与细胞众多信号通路.本文对H2O2、SRX及PRX各自的功能进行综述,还进一步探讨三者构成的信号环路对肿瘤的调控机制,从而了解该环路在肿瘤发生发展中所发挥的作用.
Oxygen free radicals（ROS） are produced through many ways in tissues,while more ROS accumulated in tumor cells,which induced oxidative stress and other factors.Hydrogen peroxide（H2O2）is a kind of vital ROS and plays dual role in our cells：cell injury and toxicity messenger.As a messenger,H2O2 involved in normal cell signal transduction and promoted the tumor oncogenesis and tumor progression.The nuclear transcription factors of AP-1（activator protein 1） and Nrf – 2（NF-E2-related factor 2） could be activated by ROS,and then combined with the upstream regulation sequence of sulfiredoxin（SRX） gene promoter.This process resulted in a up-regulation of SRX in protein level.Subsequently,the activity of specific subtype peroxiredoxin（PRX） was affected by SRX directly.The activated PRX could regulate H2O2 concentration.SRX combined with PRX to form an axis,which involved in the generation and elimination of H2O2.It may be inferred that there is an important loop compose of SRX-PRX axis and intracellular H2O2.This circuit participated in regulating cells signaling from multi-dimension.The function of H2O2,PRX and SRX are reviewed.We are also interested in exploring the correlation between the circuit and tumor and indicating the possible regulatory mechanisms to further understand its effect on tumor initiation and progression.
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2015年第4期360-366,共7页
Chinese Journal of Biochemistry and Molecular Biology
