Pretreatment with Retro-2 protects cells from death caused by ricin toxin by retaining the capacity of protein synthesis
Pretreatment with Retro-2 protects cells from death caused by ricin toxin by retaining the capacity of protein synthesis
复制标题
Retro-2 预处理通过保留蛋白质合成能力来保护细胞免遭蓖麻毒素引起的死亡
DOI：
10.1002/jat.3997
复制
发表时间：
2020-05-30
影响因子：
3.3
通讯作者：
Yang, Huiying
中科院分区：
文献类型：
--
作者：
Jiao, Zhouguang;Ke, Yuehua;Yang, Huiying
本研究旨在探讨Retro-2对蓖麻毒素(RT)细胞毒性的解毒作用及其机制，为其后续临床应用提供依据。以小鼠来源的单核巨噬细胞系RAW264.7为研究对象，通过检测细胞存活率、蛋白质合成能力、细胞因子表达以及内质网应激(ERS)相关基因的表达来评价Retro-2对RT的解毒作用。结果表明，当RT>；浓度为50 ng/mL时，许多细胞死亡。200 ng/mLRT作用2小时后，细胞蛋白质合成能力下降。此外，200 ng/mLRT作用12h或更长时间后，多种细胞因子的合成和释放减少，而细胞因子或ERS相关mRNA的表达增加。然而，与未经Retro-2处理的细胞相比，经20 mM Retro-2处理和RT刺激的细胞存活率、蛋白质合成能力和许多细胞因子的释放水平较高，而细胞因子或ERS相关mRNA的表达水平较低。综上所述，Retro-2保留了RT抑制的蛋白质合成能力，减轻了RT诱导的ERS，提高了RT攻击后细胞的活力。Retro-2显示了临床应用的潜力。
The current study explores the detoxification effect of Retro-2 on ricin toxin (RT) cytotoxicity, as well as the mechanisms underlying such effects, to provide a basis for follow-up clinical applications of Retro-2. The mouse-derived mononuclear/macrophage cell line, RAW264.7, was used to evaluate the detoxification effect of Retro-2 on RT by detecting cell viability, capacity for protein synthesis and the expression of cytokines, as well as endoplasmic reticulum stress (ERS)-related mRNA. The results indicated that many cells died when challenged with concentrations of RT >= 50ng/mL. The protein synthesis capacity of cells decreased when challenged with 200ng/mL RT for 2hours. Furthermore, the synthesis and release of many cytokines decreased, while the expression of cytokines or ERS-related mRNA increased when challenged with 200ng/mL of RT for 12 or more hours. However, cell viability, capacity for protein synthesis and release levels of many cytokines were higher, while the expression levels of cytokine, or ERS-related mRNA, were lower in cells pretreated with 20 mu m Retro-2 and challenged with RT, compared with those that had not been pretreated with Retro-2. In conclusion, Retro-2 retained the capacity for protein synthesis inhibited by RT, alleviated ERS induced by RT and increased the viability of cells challenged with RT. Retro-2 shows the potential for clinical applications.