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Effects of autophagy inducers on recombinant antibody production in insect cells
Cytotechnology ( IF 2.0 ) Pub Date : 2020-09-29 , DOI: 10.1007/s10616-020-00423-6
Ryou Nakanuma 1 , Kyoko Masumi-Koizumi 1 , Yuki Ohmuro-Matsuyama 1 , Tomohisa Katsuda 1 , Hideki Yamaji 1
Affiliation  

Insect cells have recently proven to be an excellent platform for the high-level production of functional recombinant proteins. Autophagy is an important mechanism that promotes cell survival by eliminating damaged organelles and protein aggregates, and it also may influence recombinant protein production. In the present study, we compared the effects that autophagy inducers rapamycin, everolimus, and lithium chloride exert on recombinant lepidopteran insect cells that secrete an engineered antibody molecule. Compared with nontreatment, treatment with either rapamycin or everolimus prolonged cell growth to allow high cell density, improved viability in the declining phase, and then increased the yield of secreted antibodies. These positive effects appeared to be induced via autophagy since autophagosomes were clearly detected, particularly in cells treated with rapamycin or everolimus. Unlike rapamycin, another autophagy inducer, FK506, was ineffective in insect cells. The addition of an appropriate autophagy inducer may be effective in increasing the productivity of recombinant proteins in insect cells.



中文翻译:


自噬诱导剂对昆虫细胞重组抗体产生的影响



最近,昆虫细胞被证明是高水平生产功能性重组蛋白的绝佳平台。自噬是通过消除受损细胞器和蛋白质聚集体来促进细胞存活的重要机制,并且还可能影响重组蛋白质的产生。在本研究中,我们比较了自噬诱导剂雷帕霉素、依维莫司和氯化锂对分泌工程抗体分子的重组鳞翅目昆虫细胞的影响。与未治疗相比,雷帕霉素或依维莫司治疗可延长细胞生长,从而实现高细胞密度,提高衰退期的活力,然后增加分泌抗体的产量。这些积极作用似乎是通过自噬诱导的,因为可以清楚地检测到自噬体,特别是在用雷帕霉素或依维莫司处理的细胞中。与雷帕霉素不同,另一种自噬诱导剂 FK506 在昆虫细胞中无效。添加适当的自噬诱导剂可能有效提高昆虫细胞中重组蛋白的生产力。

更新日期:2020-09-30
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