Quantitative proteomic analysis of cyclosporine-induced toxicity in a human kidney cell line and comparison with tacrolimus

Lamoureux, Fabien; Mestre, Elodie; Essig, Marie; Sauvage, François‐Ludovic; Marquet, Pierre; Gastinel, Louis N.

doi:10.1016/j.jprot.2011.09.005

Cited by 39 publications

(57 citation statements)

References 60 publications

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“…5,6 Importantly and interestingly, the direction of the fluctuations was often opposite to that found in the cited researchers' experiments.…”

Section: Discussionmentioning

confidence: 66%

“…18 Lamoureux et al found no effect of tacrolimus on the expression of H-FABP. 5 In the TMG group, we observed lower expression of cytoplasmic actin and the MUP. Lamoureux et al found no effect of tacrolimus on the expression of actin.…”

Section: Discussionmentioning

confidence: 71%

“…4 Other researchers did not observe such changes. 5,6 In the TMG group, the expression of NADH oxidoreductase was significantly lower compared to expression in the control group. Klawitter et al found no change in the expression of this protein in a group receiving tacrolimus.…”

Section: Discussionmentioning

confidence: 86%

“…4 In turn, Lamoureux et al compared the effects of cyclosporin A and tacrolimus on human embryonic kidney (HEK) cells and proved that cyclosporin A affected protein expression more significantly than tacrolimus did. 5 In the same study, respiratory chain and cytoskeletal protein expression was also affected. Klawitter et al observed similar changes in protein expression in Wistar rats treated with cyclosporin A and tacrolimus.…”

Section: Kędzierska Et Almentioning

confidence: 85%

“…Lamoureux et al found no effect of tacrolimus on the expression of actin. 5 According to Klawitter's study, tacrolimus does not contribute to altered expression of the MUP. 6 The TMG group had higher expression of cytoplasmic isocitrate dehydrogenase, triose-phosphate isomerase, and aminoacylase compared to expression in the CMG group.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Immunosuppressive Treatment On Protein Expression in Rat Kidney.

et al. 2014

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Abstract:The structural proteins of renal tubular epithelial cells may become a target for the toxic metabolites of immunosuppressants. These metabolites can modify the properties of the proteins, thereby affecting cell function, which is a possible explanation for the mechanism of immunosuppressive agents' toxicity. In our study, we evaluated the effect of two immunosuppressive strategies on protein expression in the kidneys of Wistar rats. Fragments of the rat kidneys were homogenized after cooling in liquid nitrogen and then dissolved in lysis buffer. The protein concentration in the samples was determined using a protein assay kit, and the proteins were separated by two-dimensional electrophoresis. The obtained gels were then stained with Coomassie Brilliant Blue, and their images were analyzed to evaluate differences in protein expression. Identification of selected proteins was then performed using mass spectrometry. We found that the immunosuppressive drugs used in popular regimens induce a series of changes in protein expression in target organs. The expression of proteins involved in drug, glucose, amino acid, and lipid metabolism was pronounced. However, to a lesser extent, we also observed changes in nuclear, structural, and transport proteins' synthesis. Very slight differences were observed between the group receiving cyclosporine, mycophenolate mofetil, and glucocorticoids (CMG) and the control group. In contrast, compared to the control group, animals receiving tacrolimus, mycophenolate mofetil, and glucocorticoids (TMG) exhibited higher expression of proteins responsible for renal drug metabolism and lower expression levels of cytoplasmic actin and the major urinary protein. In the TMG group, we observed higher expression of proteins responsible for drug metabolism and a decrease in the expression of respiratory chain enzymes (thioredoxin-2) and markers of distal renal tubular damage (heart fatty acid-binding protein) compared to expression in the CMG group. The consequences of the reported changes in protein expression require further study.

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“…5,6 Importantly and interestingly, the direction of the fluctuations was often opposite to that found in the cited researchers' experiments.…”

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 86%

Section: Kędzierska Et Almentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of Immunosuppressive Treatment On Protein Expression in Rat Kidney.

et al. 2014

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Current Pathways for Immune Manipulation

Lees

Azimzadeh

Ding

et al. 2014

Textbook of Organ Transplantation

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Proteomics in mechanistic toxicology: History, concepts, achievements, caveats, and potential

Rabilloud

Lescuyer

2014

Proteomics

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Toxicoproteomics can be defined as the application of proteomic approaches to the understanding of toxicology problems, and this review deals with the various types of applications that have been described in the literature. Toxicoproteomics has been applied to very different classes of toxicants, from drugs and natural products to metals, or from industrial chemicals to nanoparticles and nanofibers. It has also been applied to address questions at different levels, from the search of the primary molecular targets of toxicants to the deciphering of the molecular responses of cells and tissues to toxicants. Although restricted to mammalian cells and tissues, this paper reviews these two levels of investigation and the different application areas of toxicoproteomics, leading to the discussion of the advantages and drawbacks of the most popular proteomic platforms. Some of the pending questions in toxicoproteomics are also critically addressed, such as the specificity, validation, and result hierarchization issues. The question of shared mechanisms, which are encountered in many toxicoproteomic papers dealing with different toxicants, is also discussed. Finally, the future of toxicoproteomics is briefly outlined.

show abstract

Quantitative proteomic analysis of cyclosporine-induced toxicity in a human kidney cell line and comparison with tacrolimus

Cited by 39 publications

References 60 publications

Effects of Immunosuppressive Treatment On Protein Expression in Rat Kidney.

Effects of Immunosuppressive Treatment On Protein Expression in Rat Kidney.

Current Pathways for Immune Manipulation

Proteomics in mechanistic toxicology: History, concepts, achievements, caveats, and potential

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