title: Expression of sodium-dependent dicarboxylate transporter 1 (NaDC1/SLC13A2) in normal and neoplastic human kidney.
abstract: Regulated dicarboxylate transport is critical for acid-base homeostasis, prevention of calcium nephrolithiasis, regulation of collecting duct sodium chloride transport, and the regulation of blood pressure. Although luminal dicarboxylate reabsorption via NaDC1 (SLC13A2) is believed to be the primary mechanism regulating renal dicarboxylate transport, the specific localization of NaDC1 in the human kidney is currently unknown. This study's purpose was to determine NaDC1's expression in normal and neoplastic human kidneys. Immunoblot analysis demonstrated NaDC1 expression with an apparent molecular weight of ~61 kDa. Immunohistochemistry showed apical NaDC1 immunolabel in the proximal tubule of normal human kidney tissue; well-preserved proximal tubule brush border was clearly labeled. Apical NaDC1 expression was evident throughout the entire proximal tubule, including the initial proximal convoluted tubule, as identified by origination from the glomerular tuft, and extending through the terminal of the proximal tubule, the proximal straight tubule in the outer medulla. We confirmed proximal tubule localization by colocalization with the proximal tubule specific protein, NBCe1. NaDC1 immunolabel was not detected other than in the proximal tubule. In addition, NaDC1 immunolabel was not detected in tumors of presumed proximal tubule origin, clear cell and papillary renal cell carcinoma, or in tumors of nonproximal tubule origin, oncocytoma and chromophobe carcinoma. In summary,1) in the human kidney, apical NaDC1 immunolabel is present throughout the entire proximal tubule, and is not detectable in other renal cells; and2) NaDC1 immunolabel is not present in renal tumors. These studies provide important information regarding NaDC1's role in human dicarboxylate metabolism.
authors.affiliation: Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Handlogten
authors.affiliation: Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Gunars
authors.initials: G
authors.lastname: Osis
authors.affiliation: Department of Pathology, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: William L
authors.initials: WL
authors.lastname: Clapp
authors.affiliation: Department of Pathology, University of Florida College of Medicine, Gainesville, Florida; and.
authors.forename: Dara N
authors.initials: DN
authors.lastname: Wakefield
authors.affiliation: Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida.
authors.forename: Jill W
authors.initials: JW
authors.lastname: Verlander
authors.affiliation: Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida; David.weiner@medicine.ufl.edu.|Nephrology and Hypertension Section, Gainesville Veterans Affairs Medical Center, Gainesville, Florida.
authors.forename: I David
authors.identifier: 0000-0002-0046-0600
authors.initials: ID
authors.lastname: Weiner
mesh_terms: D015153:Blotting, Western; D029382:Dicarboxylic Acid Transporters / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000737:chemistry* / Q000473:pathology; D008871:Microvilli / Q000737:chemistry; D008970:Molecular Weight; D029363:Organic Anion Transporters, Sodium-Dependent / Q000032:analysis*; D027982:Sodium-Bicarbonate Symporters / Q000032:analysis; D027981:Symporters / Q000032:analysis*
chemical_list: D029382:Dicarboxylic Acid Transporters; D029363:Organic Anion Transporters, Sodium-Dependent; C092524:SLC13A2 protein, human; C498898:SLC4A4 protein, human; D027982:Sodium-Bicarbonate Symporters; D027981:Symporters
keywords: NaDC1; citrate; human; proximal tubule