Disturbances of calcium homeostasis within the endoplasmic reticulum may contribute to the development of ischemic-cell damage.
It is widely accepted that disturbances of calcium homeostasis play a key role in the development of cell damage produced by transient cerebral ischemia. It is believed that the sharp increase in cytosolic calcium activity during ischemia activates a cascade of calcium-dependent metabolic processes which ultimately destroy the integrity of the cell. However, it has never been taken into account that ischemic cell damage may, at least in part, be caused by a disturbance of calcium homeostasis within the endoplasmic reticulum after transient cerebral ischemia. In fact, depletion of the endoplasmic reticulum from calcium induces metabolic changes resembling, in many respects, those produced by transient cerebral ischemia: it causes an inhibition of the activity of the eucaryotic initiation factor elF-2 alpha (by phosphorylation), a disaggregation of polyribosomes and thus an inhibition of global protein synthesis, and an increased expression of certain genes such as transcription factors (c-fos and c-jun) and the glucose-related protein grp78. Finally, a depletion of calcium in the endoplasmic reticulum induces tissue damage within the brain and triggers apoptosis in neuronal and non-neuronal cells. It is therefore concluded that cell damage induced by transient ischemia may, at least in part, be caused by a disturbance of calcium homeostasis within the endoplasmic reticulum.
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