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Glutamyl aminopeptidase in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats

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dc.contributor.authorQuesada, Andrés
dc.contributor.authorSegarra, Ana Belén
dc.contributor.authorMontoro-Molina, Sebastián
dc.contributor.authorde Gracia, María Del Carmen
dc.contributor.authorOsuna, Antonio
dc.contributor.authorO'Valle, Francisco
dc.contributor.authorGómez-Guzmán, Manuel
dc.contributor.authorVargas, Félix
dc.contributor.authorWangensteen, Rosemary
dc.contributor.authoraffiliation[Quesada,A; de Gracia,MC; Osuna,A] Unidad de Nefrología, Hospital Virgen de las Nieves, FIBAO, Granada, Spain. [Segarra,AB; Montoro-Molina,S; Gómez-Guzmán,M; Wangensteen,R] Área de Fisiología, Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain. [O’Valle,F] Departamento de Anatomía Patológica, IBIMER, Universidad de Granada, Granada, Spain. [Vargas,F] Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
dc.date.accessioned2017-05-30T09:32:39Z
dc.date.available2017-05-30T09:32:39Z
dc.date.issued2017-04-11
dc.description.abstractPURPOSE: The aim of this work was to investigate if the content of glutamyl aminopeptidase (GluAp) in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats. METHODS: Urine samples were collected 24 hours after injection of cisplatin (7 mg/kg, n = 10) or saline serum (n = 10), and they were subjected to differential centrifugation at 1.000, 17.000 and 200.000 g to obtain microvesicular and exosomal fractions. GluAp was measured with a commercial ELISA kit in both fractions. Serum creatinine (SCr) and body weight were measured 15 days after treatment. We analyzed if early excretion of GluAp in microsomal and exosomal fractions was correlated with final SCr and body weight increase. In a second experiment, enzymatic activities of GluAp and alanyl aminopeptidase (AlaAp) in urine, microvesicular and exosomal fractions were measured three days after injection. We analyzed the correlation of both markers with SCr determined at this point. Finally, we studied the expression of GluAp and extracellular vesicles markers Alix and tumor susceptibility gene (TSG101) in both fractions by immunoblotting. RESULTS: GluAp excretion was increased in all fractions of urine after cisplatin treatment, even if data were normalized per mg of creatinine, per body weight or per total protein content of each fraction. We found significant predictive correlations with SCr concentration, and inverse correlations with body weight increase determined 15 days later. Three days after injection, aminopeptidasic activities were markedly increased in all fractions of urine in cisplatin-treated rats. The highest correlation coefficient with SCr was found for GluAp in microvesicular fraction. Increase of GluAp in microvesicular and exosomal fractions from cisplatin-treated rats was confirmed by immunoblotting. Alix and TSG101 showed different patterns of expression in each fraction. CONCLUSIONS: Determination of GluAp content or its enzymatic activity in microvesicular and exosomal fractions of urine is an early and predictive biomarker of renal dysfunction in cisplatin-induced nephrotoxicity. Measurement of GluAp in these fractions can serve to detect proximal tubular damage independently of glomerular filtration status.es_ES
dc.description.sponsorshipThis study was supported by the grants PI13/02743 (AO) and PI13/02384 (RW) from the Carlos III Health Institute of Spain, and the Red de Investigación Renal REDinREN RD16/0009/0033 (AO).“FEDER una manera de hacer Europa”.es_ES
dc.description.versionYeses_ES
dc.identifier.citationQuesada A, Segarra AB, Montoro-Molina S, de Gracia MD, Osuna A, O'Valle F, et al. Glutamyl aminopeptidase in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats.PLoS One. 2017;12(4):e0175462.es_ES
dc.identifier.doi10.1371/journal.pone.0175462es_ES
dc.identifier.essn1932-6203
dc.identifier.pmid28399178es_ES
dc.identifier.urihttp://hdl.handle.net/10668/2689
dc.journal.titlePloS One
dc.language.isoen
dc.publisherPublic Library of Sciencees_ES
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175462es_ES
dc.rights.accessRightsopen access
dc.subjectAnimaleses_ES
dc.subjectAntígenos CD13es_ES
dc.subjectPeso corporales_ES
dc.subjectCentrifugaciónes_ES
dc.subjectCisplatinoes_ES
dc.subjectCreatininaes_ES
dc.subjectTécnicas para inmunoenzimases_ES
dc.subjectEspacio extracelulares_ES
dc.subjectGlutamil aminopeptidasaes_ES
dc.subjectPruebas de función renales_ES
dc.subjectNeoplasiases_ES
dc.subjectRatases_ES
dc.subjectAumento de pesoes_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animalses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Exopeptidases::Aminopeptidases::Antigens, CD13es_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weightes_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Centrifugationes_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Chlorine Compounds::Cisplatines_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Imidazoles::Creatininees_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniqueses_ES
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Cellular Structures::Extracellular Spacees_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Exopeptidases::Aminopeptidases::Glutamyl Aminopeptidasees_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoblottinges_ES
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Urological::Kidney Function Testses_ES
dc.subject.meshMedical Subject Headings::Diseases::Neoplasmses_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Ratses_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Growth::Body Size::Body Weight::Body Weight Changes::Weight Gaines_ES
dc.titleGlutamyl aminopeptidase in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated ratses_ES
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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