Endoplasmic reticulum, Bcl-2 and Ca2+ handling in apoptosis.
In the complex signalling interplay that allows extracellular signals to be decoded into activation of apoptotic cell death, Ca(2+) plays a significant role. This is supported not only by evidence linking alterations in Ca(2+) homeostasis to the triggering of apoptotic (and in some cases necrotic) cell death, but also by recent data indicating that a key anti-apoptotic protein, Bcl-2, has a direct effect on ER Ca(2+) handling. We will briefly summarise the first aspect, and describe in more detail these new data, demonstrating that (i) Bcl-2 reduces the state of filling of the ER Ca(2+) store and (ii) this Ca(2+) signalling alteration renders the cells less sensitive to apoptotic stimuli. Overall, these results suggest that calcium homeostasis may represent a pharmacological target in the fundamental pathological process of apoptosis.
Ferrari
D
D
Department of Experimental Medicine, Section of General Pathology, Telethon Center for Cell Imaging, Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Via Borsari 46, I-44100, Ferrara, Italy.
Pinton
P
P
Szabadkai
G
G
Chami
M
M
Campanella
M
M
Pozzan
T
T
Rizzuto
R
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; D002118:Calcium