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1 November 2000 Identification of Potassium-Dependent and -Independent Components of the Apoptotic Machinery in Mouse Ovarian Germ Cells and Granulosa Cells
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Recent studies with thymocytes have suggested a critical role for intracellular potassium in the regulation of apoptosis. In this study, we examined the pathways of K regulation during ovarian cell death. In initial studies, fluorographic analysis demonstrated a significant loss of K during apoptosis stimulated by doxorubicin in oocytes and trophic hormone deprivation in granulosa cells. In oocytes, suppression of potassium efflux by potassium-enriched medium prevented condensation, budding, and fragmentation, although it did not block DNA degradation, suggesting the existence of potassium-independent nucleases in oocytes. Culture of granulosa cells in potassium-enriched medium inhibited internucleosomal DNA cleavage, although high-molecular weight DNA cleavage was apparent, suggesting that the nuclease or nucleases responsible for generating 50-kilobase (kb) fragments in these cells is potassium independent. To address this directly, isolated granulosa cell nuclei were stimulated to autodigest their DNA, and internucleosomal, but not large-fragment, cleavage was completely blocked by 150 mM potassium. We next examined whether the proapoptotic caspases are targets for potassium regulation. In cell-free assays, processing of pro-interleukin-1β and proteolysis of cellular actin by recombinant caspase-1 and caspase-3, respectively, were suppressed by the presence of 150 mM potassium. Other monovalent ions (NaCl, LiCl) exerted a similar effect in these cell-free assays. Thus, in oocytes and granulosa cells, potassium efflux appears to occur early in the cell death program and may regulate a number of apoptotic events including caspase activity and internucleosomal DNA cleavage. However, there also exist novel potassium-independent pathways in both ovarian germ cells and somatic cells that signal certain apoptotic events, such as large-fragment DNA cleavage.

Gloria I. Perez, Daniel V. Maravei, Alexander M. Trbovich, John A. Cidlowski, Jonathan L. Tilly, and Francis M. Hughes, Jr "Identification of Potassium-Dependent and -Independent Components of the Apoptotic Machinery in Mouse Ovarian Germ Cells and Granulosa Cells," Biology of Reproduction 63(5), 1358-1369, (1 November 2000).
Received: 8 March 2000; Accepted: 1 June 2000; Published: 1 November 2000

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