Depletion of intracellular Ca2+ by caffeine and ryanodine induces apoptosis of Chinese hamster ovary cells transfected with ryanodine receptor

Recent studies have suggested a central role for Ca2+ in the signaling path way of apoptosis and certain anti-apoptotic effects of Bcl-2 family of prot eins have been attributed to changes in intracellular Ca2+ homeostasis, Her e we report that depletion of Ca2+ from endoplasmic reticulum (ER) leads to apoptosis in Chinese hamster ovary cells. Stable expression of ryanodine r eceptor (RyR) in these cells enables rapid and reversible changes of both c ytosolic Ca2+ and ER Ca2+ content via activation of the RyR/Ca2+ release ch annel by caffeine and ryanodine. Sustained depletion of the ER Ca2+ store l eads to apoptosis in Chinese hamster ovary cells, whereas co-expression of Bcl-xL and RyR in these cells prevents apoptotic cell death but not necroti c cell death. The anti-apoptotic effect of Bcl-xL does not correlate with c hanges in either the Ca2+ release process from the ER or the capacitative C a2+ entry through the plasma membrane. The data suggest that Bcl-xL likely prevents apoptosis of cells at a stage downstream of ER Ca2+ release and ca pacitative Ca2+ entry.