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標題: The Role of Endoplasmic Reticulum Stress-Related Unfolded Protein Response in the Radiocontrast Medium-Induced Renal Tubular Cell Injury
作者: Wu, C.T.
Sheu, M.L.
Tsai, K.S.
Weng, T.I.
Chiang, C.K.
Liu, S.H.
關鍵字: contrast medium;ER stress;unfolded protein response;apoptosis;radiographic contrast-media;induced nephropathy;induced apoptosis;tumor-development;n-acetylcysteine;oxidant stress;llc-pk1 cells;er;stress;analog;proliferation
Project: Toxicological Sciences
期刊/報告no:: Toxicological Sciences, Volume 114, Issue 2, Page(s) 295-301.
Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect may have a role in the pathophysiology of CM-induced nephropathy. CM has been shown to affect the endoplasmic reticulum (ER) related capacity. Unfolded protein response (UPR) is known as a prosurvival response to reduce the accumulation of unfolded proteins and restore normal ER function. However, the role of ER stress related UPR in the CM-induced renal cell injury still remains unclear. In this study, we examined whether UPR participates in urografin (an ionic CM)-induced renal tubular cells apoptosis. Treatment with urografin in normal rat renal tubular cell line (NRK52E) markedly increased cell apoptosis and decreased cell viability with a dose- and time-dependent manner. The cell necrosis was not increased in urografin-treated cells. Urografin also enhance the induction of ER stress related markers in NRK52E cells, including glucose-regulated protein (GRP)78 and GRP94 expressions, procaspase-12 cleavage, phosphorylation of PERK (PKR [double-stranded RNA activated protein kinase]-like ER kinase), and eukaryotic initiation factor 2 alpha (eIF2 alpha). Salubrinal, a selective inhibitor of eIF2 alpha dephosphorylation, effectively decreased urografin-induced cell apoptosis. Furthermore, transfection of GRP78-small interfering RNA in NRK52E cells significantly enhanced urografin-induced cell apoptosis. These results suggest that GRP78/eIF2 alpha-related signals play a protective role during UPR, and the activation of ER stress related UPR may play an important regulative role in urografin-induced renal tubular injury.
ISSN: 1096-6080
DOI: 10.1093/toxsci/kfq006
Appears in Collections:生物醫學研究所

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