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Abstract：
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 20μm 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.
摘要：
本研究探讨了Retro-2对蓖麻毒素（RT）细胞毒性的解毒作用，以及这种影响的潜在机制，为Retro-2的后续临床应用提供依据。小鼠来源的单核/巨噬细胞系，RAW264.7，通过检测细胞活力来评估Retro-2对RT的解毒作用，蛋白质合成和细胞因子表达的能力，以及内质网应激（ERS）相关的mRNA。结果表明，当RT浓度≥50ng/mL时，许多细胞死亡。当用200ng/mLRT攻击2小时时，细胞的蛋白质合成能力降低。此外，许多细胞因子的合成和释放减少，而当用200ng/mL的RT攻击12小时或更长时间时，细胞因子或ERS相关mRNA的表达增加。然而,细胞活力，许多细胞因子的蛋白质合成和释放水平较高，而细胞因子的表达水平，或ERS相关mRNA，在用20μmRetro-2预处理并用RT攻击的细胞中，与未经Retro-2预处理的那些相比。总之,Retro-2保留了RT抑制的蛋白质合成能力，减轻RT诱导的ERS，增加RT攻击细胞的活力。Retro-2显示了临床应用的潜力。
