在稳定转染的CHO细胞中增加了糖蛋白激素产量,使用人血清白蛋白信号用于β链
Maria V Sinegubova1, Denis E Kolesov1, Ivan I Vorobiev1
1Laboratory of Mammalian Cell Bioengineering, Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia.
PeerJ
|February 18, 2025
概括
通过使用异质信号,研究人员在细胞培养中增强了关键人类葡萄糖蛋白激素的产生. 人体血清白蛋白信号显著提高了卵泡刺激激素,黄素化激素和甲状腺刺激激素的产量.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 哺乳动物细胞培养对于生产重组蛋白质至关重要,包括治疗性激素.
- 优化蛋白质表达水平对于高效的生物制药制造至关重要.
- 信号在蛋白质分泌和细胞处理中起着至关重要的作用.
研究的目的:
- 为了研究异质信号对人类异质二元糖蛋白激素的表达的影响.
- 确定最有效的信号来增强CHO细胞中重组糖蛋白激素的产生.
- 阐明生产率上升背后的机制.
主要方法:
- 中国仓鼠卵巢 (CHO) 细胞的稳定转移,其中包含编码四种人类异构体糖蛋白激素的基因.
- 利用各种信号,为这些激素的β子单元.
- 使用西式涂抹和定量PCR量化蛋白位.
主要成果:
- 来自人血清白蛋白的信号表明了在测试的葡萄糖蛋白激素家族中最高的疗效.
- 对于黄蛋白化激素 (LH;4倍),甲状腺刺激激素 (TSH;13倍) 和胆管性腺激素 (CG;60%) 观察到细胞特异性生产力的显著增加.
- 生产力增长与激素β子单元的转化和转移到内 плазма网膜的增强相关.
结论:
- 异质信号,特别是来自人类血清白蛋白,可以显著改善哺乳动物细胞中复合型葡萄糖蛋白激素的产生.
- 这种策略提供了一种可行的方法来增加重要的治疗激素如LH,TSH和CG的产量.
- 蛋白质合成和运输在内质网膜中的提高效率是观察到的生产率改善的关键.
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