Department of Toxicology (FAFY), Faculty of Medicine and Pharmacy, Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium,
Arch Toxicol. 2014 Feb;88(2):199-212. doi: 10.1007/s00204-013-1123-4. Epub 2013 Sep 8.
Apoptosis not only plays a key role in physiological demise of defunct hepatocytes, but is also associated with a plethora of acute and chronic liver diseases as well as with hepatotoxicity. The present paper focuses on the modelling of this mode of programmed cell death in primary hepatocyte cultures. Particular attention is paid to the activation of spontaneous apoptosis during the isolation of hepatocytes from the liver, its progressive manifestation upon the subsequent establishment of cell cultures and simultaneously to strategies to counteract this deleterious process. In addition, currently applied approaches to experimentally induce controlled apoptosis in this in vitro setting for mechanistic research purposes and thereby its detection using relevant biomarkers are reviewed.
细胞凋亡不仅在死亡的肝细胞的生理死亡中起着关键作用,而且还与多种急性和慢性肝病以及肝毒性有关。本文主要关注原代肝细胞培养中这种程序性细胞死亡方式的建模。特别关注从肝脏中分离肝细胞过程中自发细胞凋亡的激活、随后建立细胞培养时其逐渐表现,以及同时对抗这种有害过程的策略。此外,还回顾了目前在这种体外环境中用于机制研究目的的实验诱导可控细胞凋亡的应用方法,以及使用相关生物标志物检测这种凋亡的方法。