Lieberthal W, Menza S A, Levine J S
Evans Memorial Department of Medicine, Boston Medical Center, Massachusetts 02118-2393, USA.
Am J Physiol. 1998 Feb;274(2):F315-27. doi: 10.1152/ajprenal.1998.274.2.F315.
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 approximately 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 approximately 15% of control died uniformly of necrosis. In contrast, cells subjected to ATP depletion between approximately 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 by 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 (approximately 15 to 25% of control) representing a threshold that determines whether cells die by necrosis or apoptosis.
在小鼠近端肾小管（MPT）细胞原代培养物中研究了ATP耗竭诱导的细胞死亡机制。通过用抗霉素或2-脱氧葡萄糖与不同浓度的葡萄糖孵育细胞，诱导出程度从约对照水平的2%至70%不等的分级ATP耗竭。我们发现，ATP耗竭至低于对照水平约15%的细胞均死于坏死。相反，ATP耗竭至对照水平约25%至70%的细胞均死于凋亡。细胞死亡的速度与细胞ATP含量降低的程度成正比，且与细胞死亡机制无关。肾脏生长因子、表皮生长因子（EGF）和高剂量胰岛素并不能改善ATP耗竭诱导的凋亡性细胞死亡。我们得出结论，ATP耗竭可导致MPT细胞坏死或凋亡。此外，我们确定了一个狭窄的ATP耗竭范围（约为对照的15%至25%），该范围代表了一个决定细胞死于坏死还是凋亡的阈值。
