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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Preapoptotic cell stress response of primary hepatocytes.
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Preapoptotic cell stress response of primary hepatocytes.

机译：原代肝细胞的凋亡前细胞应激反应。

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Primary hepatocytes are an important in vitro model for studying metabolism in man. Caspase-9 and Bcl-2-associated X protein (Bax) are regulators of the apoptotic pathway. Here we report on the translocation of procaspase-9 and Bax from cytoplasm to nuclei as well as on dispersion of mitochondria; these processes occur after isolation of primary hepatocytes. The observed changes appear similar to those at the beginning of apoptosis; however, the isolated hepatocytes are not apoptotic for the following reasons: (1) cells have a normal morphology and function; (2) the mitochondria are energized; (3) there is no apoptosis unless it is induced by, e.g., staurosporine or nodularin. Staurosporine does not trigger apoptosis through activation of caspase-9, as its activity is detected later than that of caspase-3. We propose that the translocation of procaspase-9 and Bax into the nuclei reduces the ability to trigger apoptosis through the intrinsic apoptotic pathway. The shifts of procaspase-9 and Bax are reversible in the absence of the apoptotic trigger; the spontaneous reversion was confirmed experimentally for procaspase-9, whereas Bax shifted from the nuclei to the cytosol and mitochondria after the initiation of apoptosis. To distinguish this process from apoptosis, we call it preapoptotic cell stress response. It shares some features with apoptosis; however, it is reversible and apoptosis has to be induced in addition to this process. CONCLUSION: Knowledge on preapoptotic cell stress response is important for assessing the quality of the cells used in cell therapies, in regenerative medicine, and of those used for modeling metabolic processes.
机译：原代肝细胞是研究人体新陈代谢的重要体外模型。 Caspase-9和与Bcl-2相关的X蛋白（Bax）是细胞凋亡途径的调节剂。在这里，我们报道了procaspase-9和Bax从细胞质到细胞核的转运以及线粒体的分散。这些过程在分离原代肝细胞后发生。观察到的变化似乎与细胞凋亡开始时的变化相似。然而，由于以下原因，分离出的肝细胞没有凋亡：（1）细胞具有正常的形态和功能; （2）线粒体通电; （3）没有凋亡，除非它是由星形孢菌素或结核菌素诱导的。星形孢菌素不通过激活caspase-9来触发细胞凋亡，因为它的活性被检测到比caspase-3的活性晚。我们建议，procaspase-9和Bax易位进入细胞核可降低通过内在凋亡途径触发凋亡的能力。在没有凋亡触发的情况下，procaspase-9和Bax的变化是可逆的。实验证实了procaspase-9的自发逆转，而凋亡开始后，Bax从细胞核转移到细胞质和线粒体。为了区分此过程与凋亡，我们称其为凋亡前细胞应激反应。它具有凋亡的某些特征。然而，它是可逆的，除此过程外还必须诱导凋亡。结论：关于凋亡前细胞应激反应的知识对于评估用于细胞疗法，再生医学以及用于建模代谢过程的细胞的质量至关重要。

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