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Sci. STKE, 12 June 2001
Vol. 2001, Issue 86, p. tw10
[DOI: 10.1126/stke.2001.86.tw10]

EDITORS' CHOICE

Apoptosis Critical Calcium Levels

Many cellular signals and stresses can cause apoptosis; however, the exact mechanisms underlying the initiation and execution of programmed cell death may be different for different stimuli. Pinton et al. investigated apoptosis triggered by treatment of cultured cells with ceramide. The overexpression of Bcl-2 protected cells from this apoptotic stimulus. Protection against ceramide-induced cell death could also be achieved by treatments that decreased endoplasmic reticulum (ER) calcium, which is also noted to occur upon Bcl-2 overexpression. However, cells overexpressing the ER calcium-buffering protein calreticulin, which allows increased calcium loading in the ER and subsequent release without increasing free ER calcium, or cells overexpressing the ER calcium pump were more sensitive to ceramide toxicity. These results were interpreted that the amount of ER calcium per se was not crucial, but a signal generated from the released ER calcium was an important mediator of ceramide-induced apoptosis. Ceramide itself promotes the release of ER calcium. The authors suggest that the protection provided by Bcl-2 comes from depletion of the ER calcium stores, which prevents the release of a sufficiently high calcium signal from the ER upon ceramide exposure. This model is consistent with two simultaneous signals being required to initiate apoptosis, and Bcl-2 blocks one-half of these apoptotic signals.

P. Pinton, D. Ferrari, E. Rapizzi, F. Di Virgilio, T. Pozzan, R. Rizzuto, The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: Significance for the molecular mechanism of Bcl-2 action. EMBO J. 20, 2690-2701 (2001). [Abstract] [Full Text]

Citation: Critical Calcium Levels. Sci. STKE 2001, tw10 (2001).


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