title: Intrinsic carnosine metabolism in the human kidney.
abstract: Histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Animal studies suggest that carnosine can be metabolized within the kidney. The goal of this study was to obtain evidence of carnosine metabolism in the human kidney and to provide insight with regards to diabetic nephropathy. Expression, distribution, and localization of carnosinase-1 (CNDP1), carnosine synthase (CARNS), and taurine transporters (TauT) were measured in human kidneys. CNDP1 and CARNS activities were measured in vitro. CNDP1 and CARNS were located primarily in distal and proximal tubules, respectively. Specifically, CNDP1 levels were high in tubular cells and podocytes (20.3 ± 3.4 and 15 ± 3.2 ng/mg, respectively) and considerably lower in endothelial cells (0.5 ± 0.1 ng/mg). CNDP1 expression was correlated with the degradation of carnosine and anserine (r = 0.88 and 0.81, respectively). Anserine and carnosine were also detectable by HPLC in the renal cortex. Finally, TauT mRNA and protein were found in all renal epithelial cells. In diabetic patients, CNDP1 seemed to be reallocated to proximal tubules. We report compelling evidence that the kidney has an intrinsic capacity to metabolize carnosine. Both CNDP1 and CARNS are expressed in glomeruli and tubular cells. Carnosine-synthesizing and carnosine-hydrolyzing enzymes are localized in distinct compartments in the nephron and increased CNDP1 levels suggest a higher CNDP1 activity in diabetic kidneys.
authors.affiliation: University Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 672, 69120, Heidelberg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Peters
authors.affiliation: Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. c.q.f.klessens@lumc.nl.
authors.forename: Celine Q F
authors.initials: CQ
authors.lastname: Klessens
authors.affiliation: Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Baelde
authors.affiliation: University Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 672, 69120, Heidelberg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Singler
authors.affiliation: Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: Kimberley A M
authors.initials: KA
authors.lastname: Veraar
authors.affiliation: Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: Ana
authors.initials: A
authors.lastname: Zutinic
authors.affiliation: Department of Metabolic Regulation, Faculty of Biology, University of Warsaw, Krakowskie Przedmieście 26/28, 00-927, Warsaw, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Drozak
authors.affiliation: Department of Human Genetics, Medical University of Innsbruck, Innrain 52, Christoph-Probst-Platz, 6020, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.affiliation: University Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 672, 69120, Heidelberg, Germany.
authors.forename: Claus P
authors.initials: CP
authors.lastname: Schmitt
authors.affiliation: Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
mesh_terms: D000861:Anserine / Q000378:metabolism; D002336:Carnosine / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003929:Diabetic Neuropathies / Q000378:metabolism; D004150:Dipeptidases / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D006868:Hydrolysis; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D009399:Nephrons / Q000378:metabolism; D010453:Peptide Synthases / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000099247:Taurine Transporters
chemical_list: D000861:Anserine; D002336:Carnosine; D004150:Dipeptidases; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010453:Peptide Synthases; D012333:RNA, Messenger; D000099247:Taurine Transporters; C522928:CNDP1 protein, human; C019844:carnosine synthetase
keywords: Anserine; Carnosinase (CNDP1); Carnosine; Diabetic nephropathy; Metabolism