Proteomic Approaches in Understanding a Detected Relationship between Chemotherapy-Induced Nephrotoxicity and Cell Respiration in HK-2 Cells

Abstract

Background/Aims: Nephrotoxicity is a prominent component of the profile of chemotherapeutic agents and to date proteomics has represented the main technique to identify protein profiles in response to xenobiotic exposure. Methods: We made use of two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight analysis to evaluate chemotoxicity effects of cisplatin (CPT) and carboplatin (CB) on proteins from human renal proximal tubule epithelial cells (HK-2). Results: Tandem mass spectrometry analysis showed that ATP synthase subunit α and serine hydroxymethyltransferase were only expressed in HK-2 cells exposed to CPT. Since CPT causes damage in cellular respiration, we suggest that this might be a protective adaptation to CPT-induced nephrotoxicity. Thioredoxin-dependent peroxide reductase disappeared in the CPT group and was upregulated in the CB group, suggesting that CB exposure stimulates preventive apoptotic mechanisms. We suggest a relationship between chemotherapeutic agent-induced nephrotoxicity and cell respiration. The identification of proteins differentially expressed in HK-2 cells, when exposed to CPT and CB, not only supplies important information to understand the molecular action mechanisms, which are triggered by metal-based drugs in cell nephrotoxicity, but also can lead to the design of more effective anticancer drugs. Conclusion: These results provide important insights into the investigation of possible biomarker(s) of toxicity that could eventually reduce the side effects of chemotherapeutic agents.

LA-ICP-MS and nHPLC-ESI-LTQ-FT-MS/MS for the analysis of cisplatin–protein complexes separated by two dimensional gel electrophoresis in biological samples

“…36,37 Interestingly, the identified abundant ATP-synthase subunit a found in spots 22/52-53, was found to be expressed only in human RPTECs exposed to cisplatin, as a response to nephrotoxicity. 38 Moreover, the enzymatic activity of catalase, identified in the platinated spot 21, has been previously found to be decreased by cisplatin. 39 As can be seen in Table S2, similar results were obtained for the proteins identified in the ablated CBB-stained gel and the non-ablated silver stained gel run in parallel.…”

Regulation of Interleukin-6 in Head and Neck Squamous Cell Carcinoma Is Related to Papillomavirus Infection

“…In addition, 24 out of the 103 proteins (such as Calmodulin and ATP synthase A) that did not display a differential expression in tumor versus healthy tissue became up-or down-regulated after treatment, thus indicating the impact of chemotherapy, as previously described. 15,16 Following treatment, the HPV-16 viral load fell from 94.200 copies/10 3 cells to 3200 copies/10 3 cells in the tumor region. These data suggested that our proteomic approach is relevant.…”

ATP synthase subunit-β down-regulation aggravates diabetic nephropathy

“…Bothrops alternatus venom has also been found to significantly induce the functional renal alterations with increased Na + /K + -ATPase expression and activity in vivo 56 . Proteomic approaches have been performed to evaluate the nephrotoxicity of cisplatin on HK-2 cells and found that the expression of ATP synthase subunit α was increased in HK-2 cells exposed to cisplatin 57 . In the present study, we found that the ATP5b expressions in renal tubule cells were increased during AGEs exposure, which may reflect the demand of ATP synthesis to preserve the function of renal tubules in diabetic mice.…”