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pubmed-article:8910367pubmed:abstractTextThe 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.lld:pubmed
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pubmed-article:8910367pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:8910367pubmed:articleTitleIntracellular calcium stores are not required for Bcl-2-mediated protection from apoptosis.lld:pubmed
pubmed-article:8910367pubmed:affiliationDepartment of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.lld:pubmed
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pubmed-article:8910367pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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