The Role of Endoplasmic Reticulum Stress–Related Unfolded Protein Response in the Radiocontrast Medium–Induced Renal Tubular Cell Injury

• DOI: 10.1093/toxsci/kfq006
• Publication Date: 2010-01-13T21:05:42Z
• Authors: Cheng T. Wu; Meei L. Sheu; Keh S. Tsai; Te I. Weng; Chih K. Chiang; Shing H. Liu
• Keywords: Viability assay; Protein kinase R; Cell damage

Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This may have role in the pathophysiology of CM-induced nephropathy. CM has been shown to affect endoplasmic reticulum (ER)–related capacity. Unfolded protein response (UPR) is known as prosurvival reduce accumulation unfolded proteins and restore normal ER function. However, stress–related UPR cell injury still remains unclear. In this study, we examined whether participates urografin (an ionic CM)-induced cells apoptosis. Treatment with rat line (NRK52E) markedly increased apoptosis decreased viability dose- time-dependent manner. The necrosis was not urografin-treated Urografin also enhance induction markers NRK52E cells, including glucose-regulated (GRP)78 GRP94 expressions, procaspase-12 cleavage, phosphorylation PERK (PKR [double-stranded RNA–activated kinase]-like kinase), eukaryotic initiation factor 2α (eIF2α). Salubrinal, selective inhibitor eIF2α dephosphorylation, effectively urografin-induced Furthermore, transfection GRP78-small interfering RNA significantly enhanced These results suggest that GRP78/eIF2α-related signals play protective during UPR, activation an important regulative injury.