Mapping cyclosporine-induced changes in protein secretion by renal cells using stable isotope labeling with amino acids in cell culture (SILAC)

Journal of Proteomics
F LamoureuxM Essig

Abstract

Nephrotoxicity is an adverse event that strongly limits the use of the immunosuppressant cyclosporine in solid organ transplantation and the precise molecular mechanisms underlying this toxicity remain unclear. MS-based proteomic analysis of the secretome of HEK-293 renal cells exposed to cyclosporine was performed to identify changes in protein secretion, as a first step to discover potential biomarkers of such nephrotoxicity. To detect and quantify the perturbed proteins in the culture medium we used SILAC and nano-scale liquid chromatography followed by MALDI-TOF/TOF mass spectrometry. Among 106 proteins identified, 80 were quantified in both forward/reverse SILAC experiments and quantitative proteomic analysis revealed altered levels of expression for 24 secreted proteins. These included the down-regulation of a number of extracellular matrix/cell adhesion components, and the up-regulation of secreted cyclophilins A and B, macrophage inhibition factor and phosphatidylethanolamine-binding protein 1. These changes in protein secretion were not prevented by co-incubation with the antioxidant N-acetylcysteine, suggesting that they were not triggered by cyclosporine-induced oxidative stress. The results from the present study pr...Continue Reading

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Citations

Dec 20, 2014·Biomarkers in Medicine·Mangalee FernandoZoltan H Endre
Dec 1, 2012·Expert Review of Proteomics·Jean ArmengaudCatherine Duport
Jun 25, 2017·Clinical Science·Sandra BodeauAntoine Galmiche
Apr 10, 2014·Biological Chemistry·Henrik Hoffmann, Cordelia Schiene-Fischer
Dec 10, 2020·Pharmacogenomics and Personalized Medicine·Linda AwdishuMelanie S Joy
Apr 17, 2021·Frontiers in Immunology·Sandra GegundeLuis M Botana

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