School of Chemical and Bioprocess Engineering, and Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Republic of Ireland.
Cytotechnology. 2010 Jul;62(3):175-88. doi: 10.1007/s10616-010-9274-0. Epub 2010 May 26.
Cell death is a fundamentally important problem in cell lines used by the biopharmaceutical industry. Environmental stress, which can result from nutrient depletion, by-product accumulation and chemical agents, activates through signalling cascades regulators that promote death. The best known key regulators of death process are the Bcl-2 family proteins which constitute a critical intracellular checkpoint of apoptosis cell death within a common death pathway. Engineering of several members of the anti-apoptosis Bcl-2 family genes in several cell types has extended the knowledge of their molecular function and interaction with other proteins, and their regulation of cell death. In this review, we describe the various modes of cell death and their death pathways at molecular and organelle level and discuss the relevance of the growing knowledge of anti-apoptotic engineering strategies to inhibit cell death and increase productivity in mammalian cell culture.
细胞死亡是生物制药行业使用的细胞系中一个非常重要的问题。环境压力会激活信号级联反应，从而导致营养物质枯竭、副产物积累和化学物质等问题，这些反应会促进细胞死亡。在共同的死亡途径中，Bcl-2 家族蛋白是最著名的死亡过程关键调节剂，它们构成了细胞凋亡的关键细胞内检查点。在几种细胞类型中对几种抗凋亡 Bcl-2 家族基因的工程设计，扩展了它们的分子功能及其与其他蛋白质相互作用的知识，以及它们对细胞死亡的调控。在这篇综述中，我们描述了细胞死亡的各种模式及其在分子和细胞器水平上的死亡途径，并讨论了不断增长的抗凋亡工程策略的相关知识，这些知识可以抑制细胞死亡并提高哺乳动物细胞培养的生产力。
