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Inhibition of protein synthesis occurs in the post-ischemic reperfused kidney but the molecular mechanism of renal translation arrest is unknown. Several pathways have been identified whereby cell stress inhibits translation initiation via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2a, phospho-form eIF2a(P)]. Here, we report a 20-fold increase in eIF2a(P) in kidney homogenates following 10 min of cardiac arrest-induced ischemia and 10 min reperfusion. Using immunohistochemistry, we observed eIF2a(P) in tubular epithelial cells in both cortex and medulla, where the greatest eIF2a(P) staining was found in epithelial cells of the so-called watershed area at the corticomedullary junction. We further show that increased eIF2a(P) is accompanied by activation of the PKR-like endoplasmic reticulum eIF2a kinase (PERK). These observations indicate that renal ischemia and reperfusion induce stress to the endoplasmic reticulum and activate the unfolded protein response in renal epithelial cells. As the unfolded protein response can result alternatively in a pro-survival or pro-apoptotic outcome, the present study demonstrates an new additional mechanism involved in cell damage and/or repair in ischemic and reperfused kidney. © 2005 Elsevier B.V. All rights reserved.

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Biochimica et Biophysica Acta - Molecular Basis of Disease





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This article was published in Biochimica et Biophysica Acta - Molecular Basis of Disease, Volume 1741, Issue 3, Pages 314-324.

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