title: Proteomic approaches in understanding a detected relationship between chemotherapy-induced nephrotoxicity and cell respiration in HK-2 cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These results provide important insights into the investigation of possible biomarker(s) of toxicity that could eventually reduce the side effects of chemotherapeutic agents.
authors.affiliation: Nephrology Division, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Juliana Dinéia
authors.initials: JD
authors.lastname: Perez
authors.forename: Juliana Almada
authors.initials: JA
authors.lastname: Colucci
authors.forename: Maísa Mayumi
authors.initials: MM
authors.lastname: Sakata
authors.forename: Tatiana Sousa
authors.initials: TS
authors.lastname: Cunha
authors.forename: Danielle Yuri
authors.initials: DY
authors.lastname: Arita
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D016190:Carboplatin / Q000009:adverse effects / Q000494:pharmacology; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology*; D002945:Cisplatin / Q000009:adverse effects / Q000494:pharmacology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D012696:Glycine Hydroxymethyltransferase / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy; D054464:Peroxiredoxins / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D006180:Proton-Translocating ATPases / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D020543:Proteome; D016190:Carboplatin; D054464:Peroxiredoxins; D012696:Glycine Hydroxymethyltransferase; D006180:Proton-Translocating ATPases; D002945:Cisplatin