Intracellular K+ suppresses the activation of apoptosis in lymphocytes

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Abstract

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 intra-cellular 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 sub-population 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.

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Hughes, F. M., Bortner, C. D., Purdy, G. D., & Cidlowski, J. A. (1997). Intracellular K+ suppresses the activation of apoptosis in lymphocytes. Journal of Biological Chemistry, 272(48), 30567–30576. https://doi.org/10.1074/jbc.272.48.30567

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