Glutamyl aminopeptidase in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats
| Autor: | Manuel Gómez-Guzmán, Ana Belén Segarra, Félix Vargas, Rosemary Wangensteen, Antonio Osuna, Sebastián Montoro-Molina, María Del Carmen de Gracia, Andrés Quesada, Francisco O'Valle |
|---|---|
| Přispěvatelé: | [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. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Técnicas para inmunoenzimas Physiology Chemicals and Drugs::Inorganic Chemicals::Chlorine Compounds::Cisplatin [Medical Subject Headings] 030232 urology & nephrology lcsh:Medicine Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Growth::Body Size::Body Weight::Body Weight Changes::Weight Gain [Medical Subject Headings] Urine Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight [Medical Subject Headings] Exosomes Kidney Biochemistry Anatomy::Cells::Cellular Structures::Extracellular Space [Medical Subject Headings] Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoblotting [Medical Subject Headings] chemistry.chemical_compound 0302 clinical medicine Mathematical and Statistical Techniques Glutamil aminopeptidasa Organisms::Eukaryota::Animals [Medical Subject Headings] Medicine and Health Sciences lcsh:Science Multidisciplinary Chemistry Cisplatino Diseases::Neoplasms [Medical Subject Headings] Neoplasias Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniques [Medical Subject Headings] Body Fluids Physiological Parameters Creatinine Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 1-Ring::Azoles::Imidazoles::Creatinine [Medical Subject Headings] Physical Sciences Regression Analysis Creatinina Anatomy Cellular Structures and Organelles Statistics (Mathematics) Research Article medicine.medical_specialty Aumento de peso Excretion Renal function Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques Urological::Kidney Function Tests [Medical Subject Headings] Linear Regression Analysis Research and Analysis Methods Glutamyl Aminopeptidase Espacio extracelular Nephrotoxicity 03 medical and health sciences Ratas Internal medicine Antígenos CD13 medicine Animals Vesicles Statistical Methods Rats Wistar Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Exopeptidases::Aminopeptidases::Antigens CD13 [Medical Subject Headings] Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Centrifugation [Medical Subject Headings] Differential centrifugation lcsh:R Body Weight Biology and Life Sciences Peso corporal Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Exopeptidases::Aminopeptidases::Glutamyl Aminopeptidase [Medical Subject Headings] Kidneys Cell Biology Renal System Rats 030104 developmental biology Endocrinology Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings] Glutamyl aminopeptidase Animales Pruebas de función renal Microsome Centrifugación lcsh:Q Cisplatin Physiological Processes Biomarkers Mathematics |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 4, p e0175462 (2017) |
| ISSN: | 1932-6203 |
| Popis: | PURPOSE: 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. This 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”. Yes |
| Databáze: | OpenAIRE |
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