title: Proteomic profiling of k-11706 responsive proteins.
abstract: Erythropoietin promotes the production of red blood cells. Recombinant human erythropoietin is illicitly used to improve performance in endurance sports. Expression of the ERYTHROPOIETIN gene is negatively controlled by the transcription factor GATA-binding protein (GATA). Specific GATA inhibitors have recently been developed as novel drugs for the management of anemia. These drugs could, therefore, be illicitly used like recombinant human erythropoietin to improve performance in sports. To examine alterations in levels of plasma protein after administration of GATA inhibitors, proteomic analyses were conducted on mouse plasma samples treated with the potent GATA inhibitor K-11706. The analysis based on gel electrophoresis identified 41 protein spots differentially expressed when compared with normal plasma. Each spot was identified with liquid chromatography coupled to tandem mass spectrometry and 2 of them, fetuin-B and prothrombin, were verified by Western blotting. The results showed that the expression of fetuin-B in mice plasma was increased by K-11706, but not by recombinant human erythropoietin or hypoxia. These results suggest the potential of proteomic-based approaches as tools to identify biomarkers for the illegal use of novel drugs (e.g., GATA inhibitors). Also, fetuin-B could be a sensitive marker for the detection of abuse of GATA inhibitors.
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Department of Sports Medicine, Tsukuba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Horie
authors.forename: Y
authors.initials: Y
authors.lastname: Kawashima
authors.forename: A
authors.initials: A
authors.lastname: Naka
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: K
authors.initials: K
authors.lastname: Iida
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002853:Chromatography, Liquid; D004300:Doping in Sports; D004591:Electrophoresis, Polyacrylamide Gel; D004921:Erythropoietin / Q000494:pharmacology; D060752:Fetuin-B; D050980:GATA Transcription Factors / Q000037:antagonists & inhibitors*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D040901:Proteomics / Q000379:methods*; D011516:Prothrombin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry; D000509:alpha-Fetoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C504688:Fetub protein, mouse; D060752:Fetuin-B; D050980:GATA Transcription Factors; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; D004921:Erythropoietin; D011516:Prothrombin