ROS对FOXO蛋白激活和基因表达的影响  

ROS regulation of FOXO activity and its expression

作　　者：吕舸 周吉芳 杨杰[1] 丁启龙[1] LYU Ge;ZHOU Jifang;YANG Jie;DING Qilong(Pharmacy Experiment Teaching Center,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学医学基础实验教学中心

出　　处：《药学研究》2019年第5期286-289,310,共5页Journal of Pharmaceutical Research

摘　　要：叉头框转录因子家族O亚族(FOXO)是多种细胞内过程的重要调节因子,如能量代谢、氧化应激应答、氧化还原信号通路、细胞周期进展、凋亡等。活性氧簇(ROS)和其他能够产生活性氧簇的应激刺激能够在多个水平调节叉头框转录因子家族O亚族的激活和蛋白基因表达。一方面,从转录水平调节叉头框转录因子家族O亚族的蛋白表达,如作用于叉头框转录因子家族O亚族的上游调节蛋白p53、影响miRNA对叉头框转录因子家族O亚族mRNA的调节、影响HuR对叉头框转录因子家族O亚族mRNA的调节。另一方面也可以通过磷酸化和乙酰化等影响叉头框转录因子家族O亚族的活性、稳定和与DNA的结合。另外活性氧簇还能通过影响叉头框转录因子家族O亚族转录共激活因子调节叉头框转录因子家族O亚族蛋白激活。在与氧化应激相关的一些病理条件下,叉头框转录因子家族O亚族过度活化和过多表达会导致各种疾病,如癌症、糖尿病等的发生。因此本文综述了活性氧簇对叉头框转录因子家族O亚族活性和表达的影响,从而能够进一步明确疾病的发病机制,为研发新的药物提供思路。Forkhead box,class O(FOXO) is an important regulator of various intracellular processes in-vitro and in vivo .It regulates energy metabolism,oxidative stress response,redox signaling pathway,cell cycle progression,apoptosis,etc.Reactive oxygen species(ROS) modulates activation of FOXO and protein content at multiple levels.On one hand,ROS regulates the protein expression through p53,miRNA,HuR.whereas,on the other hand,ROS also modifies FOXO activation and stabilization,through phosphorylation,acetylation.In addition,ROS may also modulate FOXO protein activation by affecting FOXO transcriptional coactivators.Under several pathological conditions associated with oxidative stress,activation of FOXO exceeds that leads to various diseases,such as diabetes and cancer.In this review,we will discussed on the effects of ROS on FOXO activity and its expression.This will further clarify the pathogenesis of the disease and provide ideas for the development of new drugs.

关 键 词：叉头框转录因子家族O亚族 活性氧簇 活性调节 蛋白表达调节 

分 类 号：R363[医药卫生—病理学]