Radiocontrast medium induced nephrotoxicity is a major clinical problem. There is considerable interest in reducing the incidence of acute renal failure due to the use of radiocontrast media (RCM). Reduction of renal blood flow and direct toxic effect on renal tubular epithelial cells have been postulated as major causes of RCM nephropathy. Understanding the molecular mechanisms by which RCM cause cell damage may allow the development of pharmacological therapy to prevent their nephrotoxicity. In this work we have investigated the signaling pathways that may be affected by RCM. The incubation of human renal tubular proximal cells with sodium diatrizoate, iopromide and iomeprol caused a marked dephosphorylation of the kinase Akt on Ser473 within 5 min of incubation. RCM also caused a decrease in cell viability, which was substantially alleviated by transfecting the cells with a constitutively active form of Akt. Further downstream targets of Akt, including the Forkhead family of transcription factors FKHR andFKHRL1, were also dephosphorylated by RCM at Thr24 and Thr32, respectively. The P70S6 kinase was also dephosphorylated at Thr389 and Ser371 by RCM. However there was a more dramatic decrease in phosphorylation of the phosphorylated form of mammalian target of rapamycin (mTOR) and of the extracellular-signal regulated kinases (ERK) 1/2 caused by sodium diatrizoate than by iopromide. These results demonstrate the effect of RCM on some intracellular signaling pathways that may allow understanding of the mechanism of their toxicity and may allow the development of strategies to overcome their adverse effects. (c) 2006 Elsevier Inc. All rights reserved.
|Tipologia:||Articolo su rivista|
|Citazione:||Andreucci M., F.G. (2006). Radiocontrast media cause dephosphorylation of Akt and downstream signaling targets in human renal proximal tubular cells. BIOCHEMICAL PHARMACOLOGY, 72(10), 1334-1342.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||10.1016/j.bcp.2006.08.008|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2006|
|Titolo:||Radiocontrast media cause dephosphorylation of Akt and downstream signaling targets in human renal proximal tubular cells|
|Autori interni:||TOZZO, CARMELA|
|Autori:||Andreucci M., Fuiano G., Presta P., Esposito P., Faga T., Bisesti V., Procino A., Altieri V., Tozzo C., Memoli B., Michael A.|
|Appare nelle tipologie:||01 - Articolo su rivista|
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