20-hydroxyecdysone regulates expression of methioninesulfoxide reductases through transcription factor FOXO in the red flour beetle, Tribolium castaneum
20-hydroxyecdysone regulates expression of methioninesulfoxide reductases through transcription factor FOXO in the red flour beetle, Tribolium castaneum
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20-羟基蜕皮酮通过转录因子 FOXO 调节赤拟谷盗中甲硫氨酸亚砜还原酶的表达
DOI：
10.1016/j.ibmb.2021.103546
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发表时间：
2021-02-06
影响因子：
3.8
通讯作者：
Wang, Jianjun
中科院分区：
文献类型：
--
作者：
Ji, Caihong;Zhang, Nan;Wang, Jianjun
活性氧（ROS）对蛋氨酸（Met）的氧化对蛋白质功能产生不利影响。甲基亚砜还原酶（Msr）是参与蛋白质修复的二级抗氧化酶，分为两个不同的类别，MsrA和MsrB，尽管Msrs的转录调控机制仍然很大程度上未知。本研究从赤拟谷盗Tribolium castaneum中克隆了编码MsrA和MsrB的三种可变剪接异构体的全长cDNA。雌性成虫暴露于氧化，热和冷应激诱导MsrA和MsrB的表达。RNAi介导的MsrA和MsrB的敲低导致T.对百草枯诱导的氧化应激的影响。用20-羟基蜕皮激素（20 E）处理增加了MsrA和MsrB两者的表达水平。敲低转录因子叉头盒O（FOXO）可降低百草枯对MsrA和MsrB mRNA的诱导作用。荧光素酶报告基因分析显示，FOXO直接激活MsrA和MsrB的启动子。百草枯处理诱导了蜕皮激素合成基因Shade和Phantom的表达，20 E上调了FOXO的表达，促进了FOXO的核转位，而敲低FOXO则抑制了20 E对MsrA和MsrB表达的诱导，表明20 E对MsrA和MsrB的调控是由FOXO介导的。总之，这些结果提供了重要的见解昆虫Msrs的转录调控。
The oxidation of methionine (Met) by reactive oxygen species (ROS) causes detrimental effects on the protein functions. Methionine sulfoxide reductase (Msr) is the secondary antioxidant enzyme involved in protein repair, and is divided into two distinct classes, MsrA and MsrB, although the mechanisms underlying the transcriptional regulation of Msrs remain largely unknown. In this study, the full-length cDNAs encoding MsrA and three alternatively spliced isoforms of MsrB were isolated from the red flour beetle, Tribolium castaneum. Exposure of female adults to oxidative, heat and cold stresses induced expressions of both MsrA and MsrB. RNAi-mediated knockdown of MsrA and MsrB resulted in increased sensitivity of T. castaneum to paraquat-induced oxidative stress. Treatment with 20-hydroxyecdysone (20E) increased expression levels of both MsrA and MsrB. Knockdown of transcription factor forkhead box O (FOXO) decreased both MsrA and MsrB mRNA levels and abolished the induction of MsrA and MsrB by paraquat. Luciferase reporter assays revealed that FOXO directly activates the promoters of both MsrA and MsrB. Moreover, paraquat treatment induced expression of two ecdysone biosynthesis genes, Shade and Phantom, 20E upregulated exoression of FOXO, promoted FOXO nuclear translocation, and knockdown of FOXO abolished induction of MsrA and MsrB expression by 20E, suggesting that regulation of MsrA and MsrB by 20E was mediated by FOXO. Overall, these results provide important insights into the transcriptional regulation of insect Msrs.