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Volume 271, Number 44, Issue of November 1, 1996 pp. 27739-27743
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Intracellular Calcium Stores Are Not Required for Bcl-2-mediated Protection from Apoptosis

(Received for publication, July 12, 1996, and in revised form, August 5, 1996)

From the Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755

The ability of Bcl-2 to inhibit cell death is well documented but its mechanism of action remains elusive. Recent reports have suggested that Bcl-2 prevents apoptosis by inhibiting the release of Ca²⁺ from the thapsigargin-sensitive Ca²⁺ store. The mobilization of Ca²⁺ from this store has been implicated as a signal regulating apoptotic cell death induced by glucocorticoids and by interleukin-3 withdrawal. The present study was designed to determine if Bcl-2 would still inhibit apoptosis after depletion of intracellular Ca²⁺ stores. We compared the response of two Chinese hamster ovary cell lines (5AHSmyc and 5A300bcl-2.2) following incubation with the calcium ionophore ionomycin to deplete intracellular Ca²⁺ stores. Continued incubation of 5AHSmyc cells in calcium-free media induced substantial apoptotic DNA fragmentation within 4 h and >95% loss of viability within 48 h. However, 5A300bcl-2.2 cells showed no evidence of DNA fragmentation or loss of viability over the same time period. Intracellular Ca²⁺ was analyzed with the Ca²⁺-sensitive fluorescent dye INDO-1 and confirmed that ionomycin was capable of releasing Ca²⁺ from intracellular stores in both cell lines. These results show that depletion of intracellular Ca²⁺ stores induces apoptosis and that these Ca²⁺ stores are not required for the protection afforded by Bcl-2.

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