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

Autor(es)

Perez, Juliana Dineia ; Colucci, Juliana Almada ; Sakata, Maisa Mayumi ; Cunha, Tatiana Sousa ; Arita, Danielle Yuri ; Casarini, Dulce Elena

• Tipo de documento: Artigo Científico
• Fonte: NEPHRON PHYSIOLOGY; v. 119, n. 1, p. P1-P10, 2011.
• Citações Web of Science: 8

Resumo

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 alpha 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. Copyright (C) 2011 S. Karger AG, Basel (AU)

• Processo FAPESP: 05/59840-1 - Analise proteomica comparativa da celula epitelial do tubulo proximal humano (hk-2) diante dos efeitos nefrotoxicos dos agentes quimiotera picos e carboplatina.
• Beneficiário: Juliana Dinéia Perez Brandão
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 07/55799-2 - Analise proteomica comparativa da celula epitelial do tubulo proximal humano (hk-2) diante dos efeitos nefrotoxicos dos agentes quimioterapicos cisplatina e carboplatina.
• Beneficiário: Dulce Elena Casarini
• Modalidade de apoio: Auxílio à Pesquisa - Regular