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首页> 外文期刊>American Journal of Physiology >Characterization of cell clones isolated from hypoxia-selected renal proximal tubular cells.
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Characterization of cell clones isolated from hypoxia-selected renal proximal tubular cells.

机译：从缺氧选择的肾近端肾小管细胞分离的细胞克隆的表征。

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Under hypoxia, some cells survive and others are irreversibly injured and die. The factors that determine cell fate under stress remain largely unknown. We recently selected death-resistant cells via repeated episodes of hypoxia. In the present study, 80 clones were isolated from the selected cells and their response to apoptotic injury was characterized. Compared with the wild-type cells, the isolated clones showed a general resistance to apoptosis: 13 were extremely resistant to azide-induced apoptosis, 10 to staurosporine, and 9 to cisplatin. The cell clones that most consistently demonstrated resistance or sensitivity to injury were further studied for their response to azide treatment. Azide induced comparable ATP depletion in these clones and wild-type cells. Hypoxia inducible factor-1 (HIF-1) was upregulated in several clones, but the upregulation did not correlate with cell death resistance. The selected clones maintained an epithelial phenotype, showing typical epithelial morphology, forming "domes" at high density, and expressing E-cadherin. Azide-induced Bax translocation and cytochrome c release, two critical mitochondrial events of apoptosis, were abrogated in death-resistant clones. In addition, cell lysates isolated from these clones showed lower caspase activation on addition of exogenous cytochrome c. Bax, Bak, and Bid expression in these clones was similar to that in wild-type cells, whereas Bcl-2 expression was higher in all the selected clones and, interestingly, Bcl-xL was markedly upregulated in the most death-resistant clones. The results suggest that apoptotic resistance of the selected clones is not determined by a single factor or molecule but, rather, by various alterations at the core apoptotic pathway.
机译：在缺氧条件下，一些细胞存活下来，而另一些则不可逆转地受伤并死亡。在压力下决定细胞命运的因素仍然未知。我们最近通过反复缺氧事件选择了抗死亡细胞。在本研究中，从选定的细胞中分离出80个克隆，并表征了它们对凋亡的反应。与野生型细胞相比，分离出的克隆显示出对凋亡的一般抵抗力：13个对叠氮化物诱导的凋亡具有极强的抵抗力，10个对星形孢菌素具有抗性，9个对顺铂具有抗性。进一步研究了最一致显示出对损伤的抗性或敏感性的细胞克隆对叠氮化物处理的反应。叠氮化物在这些克隆和野生型细胞中诱导了相当的ATP消耗。缺氧诱导因子-1（HIF-1）在几个克隆中上调，但上调与细胞死亡抗性无关。选定的克隆保持上皮表型，表现出典型的上皮形态，高密度形成“圆顶”，并表达E-钙粘蛋白。耐死亡克隆中废除了叠氮化物诱导的Bax易位和细胞色素C释放，这是两个重要的线粒体凋亡事件。此外，从这些克隆中分离的细胞裂解物在添加外源细胞色素c后显示出较低的caspase活化。这些克隆中的Bax，Bak和Bid表达与野生型细胞中的表达相似，而Bcl-2表达在所有选定克隆中均较高，有趣的是，Bcl-xL在最耐死亡的克隆中明显上调。结果表明，所选克隆的凋亡抗性不是由单一因素或分子决定的，而是由核心凋亡途径的各种改变决定的。

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