title: Loss of endoplasmic reticulum Ca2+ homeostasis: contribution to neuronal cell death during cerebral ischemia.
abstract: The loss of Ca(2+) homeostasis during cerebral ischemia is a hallmark of impending neuronal demise. Accordingly, considerable cellular resources are expended in maintaining low resting cytosolic levels of Ca(2+). These include contributions by a host of proteins involved in the sequestration and transport of Ca(2+), many of which are expressed within intracellular organelles, including lysosomes, mitochondria as well as the endoplasmic reticulum (ER). Ca(2+) sequestration by the ER contributes to cytosolic Ca(2+) dynamics and homeostasis. Furthermore, within the ER Ca(2+) plays a central role in regulating a host of physiological processes. Conversely, impaired ER Ca(2+) homeostasis is an important trigger of pathological processes. Here we review a growing body of evidence suggesting that ER dysfunction is an important factor contributing to neuronal injury and loss post-ischemia. Specifically, the contribution of the ER to cytosolic Ca(2+) elevations during ischemia will be considered, as will the signalling cascades recruited as a consequence of disrupting ER homeostasis and function.
authors.affiliation: Department of Physiology and Pharmacology, Western University, London, Ontario, Canada.
authors.forename: Ankur
authors.initials: A
authors.lastname: Bodalia
authors.forename: Hongbin
authors.initials: H
authors.lastname: Li
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress; D006706:Homeostasis; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D056811:Unfolded Protein Response
chemical_list: D002118:Calcium