Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells
Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells
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DOI：
10.1152/ajprenal.1998.274.2.f315
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发表时间：
1998-02-01
影响因子：
4.2
通讯作者：
Levine, JS
中科院分区：
文献类型：
--
作者：
Lieberthal, W;Menza, SA;Levine, JS
在原代培养的小鼠近端肾小管（MPT）细胞中研究ATP耗竭诱导细胞死亡的机制。通过将细胞与抗霉素或2-脱氧葡萄糖（含不同浓度的葡萄糖）一起孵育，诱导了ATP的分级消耗，严重程度为对照水平的2%至70%。我们发现，细胞受到ATP耗竭低于类似于15%的控制均匀坏死。相比之下，细胞经历类似于对照的25%至70%之间的ATP耗竭，全部死于凋亡。细胞死亡的速度与细胞ATP含量减少的严重程度成正比，而与细胞死亡的机制无关。肾生长因子，表皮生长因子（EGF）和高剂量胰岛素，并没有改善ATP耗竭诱导的细胞凋亡。我们的结论是，ATP耗竭可以导致MPT细胞坏死或凋亡。此外，我们已经确定了一个狭窄的ATP消耗范围（类似于对照组的15%至25%），这代表了一个确定细胞是通过坏死还是凋亡死亡的阈值。
The mechanisms of cell death induced by ATP depletion were studied in primary cultures of mouse proximal tubular (MPT) cells. Graded ATP depletion, ranging in severity from similar to 2 to 70% of control levels, was induced by incubating cells with either antimycin or 2-deoxyglucose, with varying concentrations of dextrose. We found that cells subjected to ATP depletion below similar to 15% of control died uniformly of necrosis. In contrast, cells subjected to ATP depletion between similar to 25 and 70% of control all died by apoptosis. The rapidity of cell death was proportional to the severity of reduction of cell ATP content and was independent of the mechanism of cell death. Renal growth factors, epidermal growth factor (EGF) and high-dose insulin, did not ameliorate apoptotic cell death induced ty ATP depletion. We conclude that ATP depletion can cause either necrosis or apoptosis in MPT cells. Furthermore, we have identified a narrow range of ATP depletion (similar to 15 to 25% of control) representing a threshold that determines whether cells die by necrosis or apoptosis.