The dual role of calcium as messenger and stressor in cell damage, death, and survival

Ca^{2 +} is an important second messenger participating in many cellular activities; when physicochemical insults deregulate its delicate homeostasis, it acts as an intrinsic stressor, producing/increasing cell damage. Damage elicits both repair and death responses; intriguingly, in those responses Ca^{2 +} also participates as second messenger. This delineates a dual role for Ca^{2 +} in cell stress, making difficult to separate the different and multiple mechanisms required for Ca^{2 +} -mediated control of cell survival and apoptosis. Here we attempt to disentangle the two scenarios, examining on the one side, the events implicated in deregulated Ca^{2 +} toxicity and the mechanisms through which this elicits reparative or death pathways; on the other, reviewing the role of Ca^{2 +} as a messenger in the transduction of these same signaling events.