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Published on: October 26, 2021
Proteomic approaches in understanding a detected relationship between chemotherapy-induced nephrotoxicity and cell
Juliana Dinéia Perez1, Juliana Almada Colucci, Maísa Mayumi Sakata
1Nephrology Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
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.
Insights
Proteomics reveals distinct protein changes in kidney cells exposed to cisplatin and carboplatin, offering insights into chemotherapy-induced nephrotoxicity and potential biomarkers for safer cancer drugs.
Area of Science:
- Proteomics
- Chemotherapy
- Nephrotoxicity
Background:
- Chemotherapeutic agents often cause nephrotoxicity.
- Proteomics is key to identifying protein responses to xenobiotics.
Purpose of the Study:
- To investigate the proteomic changes in human renal proximal tubule epithelial cells (HK-2) exposed to cisplatin (CPT) and carboplatin (CB).
- To understand the molecular mechanisms of CPT- and CB-induced nephrotoxicity.
Main Methods:
- Two-dimensional gel electrophoresis (2-DE).
- Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis.
- Tandem mass spectrometry.
Main Results:
- CPT exposure led to the expression of ATP synthase subunit α and serine hydroxymethyltransferase, potentially as a protective response to cellular respiration damage.
- Thioredoxin-dependent peroxide reductase was downregulated by CPT and upregulated by CB, suggesting different apoptotic pathway activations.
- Identified differentially expressed proteins provide insights into metal-based drug nephrotoxicity mechanisms.
Conclusions:
- The study offers insights into potential biomarkers for chemotherapy-induced nephrotoxicity.
- Findings may aid in designing safer and more effective anticancer drugs with reduced side effects.
