Renal ischemia and reperfusion activates the eIF2 alpha kinase PERK

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1741

Article

Montie, HL ; Kayali, F ; Haezebrouck, AJ ; Rossi, NF ; DeGracia, DJ

关键词: renal ischemia and reperfusion;    eIF2 alpha(P);    endoplasmic reticulum stress;    PERK;    protein synthesis inhibition;    unfolded protein response;   

DOI  :  10.1016/j.bbadis.2005.04.007

来源: Elsevier

【 摘 要 】

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 (eIF2 alpha, phospho-forin eIF2 alpha(P)]. Here, we report a 20-fold increase in eIF2 alpha(P) in kidney homogenates following 10 min of cardiac arrest-induced ischemia and 10 min reperfusion. Using immunohistochemistry, we observed eIF2 alpha L(P) in tubular epithelial cells in both cortex and medulla, where the greatest eIF2 alpha(P) staining was found in epithelial cells of the so-called watershed area at the corticomedullary junction. We further show that increased eIF2 alpha(P) is accompanied by activation of the PKR-like endoplasmic reticulum eIF2 alpha 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. (c) 2005 Elsevier B.V. All rights reserved.

【 授权许可】

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