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首页> 外文期刊>Cell biology international. >Loss of Bcl-2 expression correlates with increasing sensitivity to apoptosis in differentiating ES cells.
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Loss of Bcl-2 expression correlates with increasing sensitivity to apoptosis in differentiating ES cells.

机译:Bcl-2表达的丧失与分化的ES细胞对凋亡的敏感性增加有关。

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摘要

Embryonic stem (ES) cells are derived from the inner cell mass of blastocysts and have a pluripotency to differentiate into a variety of cell types. ES cells have high resistance to environmental stress compared to functional cells, which can undergo apoptosis when stressed. We have investigated whether ES cells have resistance to multiple types of stress or selective stress. Phytosphingosine (PHS) and staurosporine (STS) were used as chemical stressors. PHS induced mitochondria-mediated apoptosis in several cell lines. STS is a protein kinase inhibitor that induces apoptosis even without mitochondrial involvement. PHS treatment damaged 3T3 mouse fibroblasts, but did not damage ES cells. STS damaged ES cells as well as 3T3 mouse fibroblasts at similar doses. Susceptibility to cell damage is correlated with the retention of the mitochondrial membrane potential. PHS treatment could induce DNA fragmentation in differentiated ES cells. Differences in cell-death susceptibility between the undifferentiated and differentiated states showed that the mitochondria-localised anti-apoptotic protein Bcl-2 was highly expressed in undifferentiated ES cells, which gradually decreased during differentiation. These results suggest that undifferentiated mouse ES cells have a high resistance to mitochondria-involved extracellular stress.
机译:胚胎干细胞(ES)源自囊胚的内部细胞团,具有多能性,可以分化为多种细胞类型。与功能性细胞相比,ES细胞对环境压力具有较高的抵抗力,而功能性细胞在受到压力时会发生凋亡。我们研究了ES细胞是否对多种压力或选择性压力具有抵抗力。植物鞘氨醇(PHS)和星形孢菌素(STS)被用作化学应激源。 PHS在几种细胞系中诱导线粒体介导的凋亡。 STS是一种蛋白激酶抑制剂,即使没有线粒体参与也能诱导凋亡。 PHS处理可损坏3T3小鼠成纤维细胞,但不会损坏ES细胞。 STS以相似的剂量破坏了ES细胞以及3T3小鼠成纤维细胞。细胞损伤的易感性与线粒体膜电位的保留相关。 PHS处理可在分化的ES细胞中诱导DNA片段化。未分化状态和分化状态之间细胞死亡敏感性的差异表明,线粒体定位的抗凋亡蛋白Bcl-2在未分化ES细胞中高度表达,并在分化过程中逐渐降低。这些结果表明,未分化的小鼠ES细胞对线粒体参与的细胞外应激具有高抗性。

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