Intracellular K+ suppresses the activation of apoptosis in lymphocytes
Intracellular K+ suppresses the activation of apoptosis in lymphocytes
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DOI：
10.1074/jbc.272.48.30567
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发表时间：
1997-11-28
影响因子：
4.8
通讯作者：
Cidlowski, JA
中科院分区：
文献类型：
--
作者：
Hughes, FM;Bortner, CD;Cidlowski, JA
细胞凋亡抑制的机制知之甚少。我们已经解决了新的可能性，细胞内K+的水平调节细胞凋亡的过程中，通过控制死亡酶的活性。我们发现，K+，在正常的细胞内水平，抑制细胞凋亡DNA片段化和caspase-3（CPP 32）样蛋白酶的激活，这表明细胞内K+的损失必须发生在细胞凋亡的早期。通过电感耦合等离子体/质谱法和流式细胞术直接测量K+表明凋亡细胞中细胞内K+浓度大幅降低。流式细胞仪分析表明，caspase和核酸酶活性仅限于细胞亚群与减少K+，破坏天然K+电化学梯度抑制caspase和核酸酶的活性独立的模式的激活的凋亡诱导剂，表明细胞内K+浓度的降低是一个必要的，在程序性细胞死亡的早期事件。
Little is known about the mechanisms of suppression of apoptosis. We have addressed the novel possibility that the level of intracellular K+ regulates the apoptotic process by controlling the activity of death enzymes. We show that K+, at normal intracellular levels, inhibits both apoptotic DNA fragmentation and caspase-3(CPP32)-like protease activation, suggesting that intracellular K+ loss must occur early during apoptosis. Direct measurement of K+ by inductively coupled plasma/ mass spectrometry and flow cytometry indicates a major decrease in intracellular K+ concentration in the apoptotic cell. Flow cytometric analysis revealed that caspase and nuclease activity were restricted to the subpopulation of cells with reduced K+, Disruption of the natural K+ electrochemical gradient suppressed the activity of both caspase and nuclease independent of the mode of activation of the apoptotic inducing agent, demonstrating that a decrease in intracellular K+ concentration is a necessary, early event in programmed cell death.