Regulation of the endoplasmic reticulum calcium storage during the unfolded protein response--significance in tissue ischemia?
Endoplasmic reticulum (ER) is an organelle intimately involved in control of cell activities through Ca(2+) signaling, as well as in post-translational protein folding and maturation. Ca(2+) storage within the ER is required for both of these functions. Several of the ER-resident proteins essential for the protein folding pathway require Ca(2+) binding for their activity. A number of factors, including Ca(2+) depletion, may interfere with the folding pathway within the ER, with a potential for cell injury through an accumulation of malfolded protein aggregates. The Unfolded Protein Response involves a transcriptional upregulation of a number of the ER-resident folding helper proteins and becomes triggered when the folding pathway is blocked. To be effective, these upregulated proteins require a sufficient supply of Ca(2+) cofactor within the ER lumen. In tissue ischemia, where the availablity of this cofactor may be compromised, the newly described ability of the cell to boost the ER Ca(2+)-loading capacity by upregulating the ER Ca(2+) pump may be of particular importance for limiting cell injury and promoting survival. The novel focus on the pathophysiological significance of ER Ca(2+)depletion extends the scope of disturbed Ca(2+) homeostasis following ischemia beyond the consequences of the cytosolic calcium overload.
Treiman
Marek
M
Department of Medical Physiology, Division of Renal and Cardiovascular Physiology, University of Copenhagen, The Panum Institute, Copenhagen, Denmark. M.Treiman@mfi.ku.dk
D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D017510:Protein Folding; D015854:Up-Regulation
D002118:Calcium