Distribution of organic anion transporters NaDC3 and OAT1-3 along the human nephron

Autor: Hrvoje Brzica, Yohannes Hagos, Birgitta C. Burckhardt, Naohiko Anzai, Nikola Radović, Davorka Breljak, Ivana Vrhovac Madunić, Dean Karaica, Daniela Balen Eror, Gerhard Burckhardt, Marija Ljubojević, Hermann Koepsell, Ognjen Kraus, Vedran Micek, Ivan Sabolić
Rok vydání: 2016
Předmět:
Adult
Male
0301 basic medicine
Organic anion transporter 1
Physiology
Organic Anion Transporters
Organic Anion Transporters
Sodium-Dependent
Nephron
Organic Anion Transporters
Sodium-Independent
Biology
03 medical and health sciences
Organic Anion Transport Protein 1
0302 clinical medicine
medicine
Humans
Kidney Tubules
Collecting
Na+/K+-ATPase
Kidney Tubules
Distal
Epithelial polarity
Dicarboxylic Acid Transporters
Kidney Medulla
Sex Characteristics
Membranes
Symporters
urogenital system
Nephrons
Middle Aged
Molecular biology
HEK293 Cells
Na+-K+-ATPase
Na+-dicarboxylate cotransporter 3
Western blotting
human kidney
immunocytochemistry
organic anion transporter 1
organic anion transporter 2
organic anion transporter 3
sex differences
species differences
030104 developmental biology
medicine.anatomical_structure
Biochemistry
Renal physiology
biology.protein
Macula densa
Female
Sodium-Potassium-Exchanging ATPase
Cotransporter
030217 neurology & neurosurgery
Immunostaining
Zdroj: American Journal of Physiology-Renal Physiology. 311:F227-F238
ISSN: 1522-1466
1931-857X
Popis: The initial step in renal secretion of organic anions (OAs) is mediated by transporters in the basolateral membrane (BLM). Contributors to this process are primary active Na+-K+-ATPase (EC 3.6.3.9), secondary active Na+-dicarboxylate cotransporter 3 (NaDC3/SLC13A3), and tertiary active OA transporters (OATs) OAT1/SLC22A6, OAT2/SLC22A7, and OAT3/SLC22A8. In human kidneys, we analyzed the localization of these transporters by immunochemical methods in tissue cryosections and isolated membranes. The specificity of antibodies was validated with human embryonic kidney-293 cells stably transfected with functional OATs. Na+-K+-ATPase was immunolocalized to the BLM along the entire human nephron. NaDC3-related immunostaining was detected in the BLM of proximal tubules and in the BLM and/or luminal membrane of principal cells in connecting segments and collecting ducts. The thin and thick ascending limbs, macula densa, and distal tubules exhibited no reactivity with the anti-NaDC3 antibody. OAT1–OAT3-related immunostaining in human kidneys was detected only in the BLM of cortical proximal tubules; all three OATs were stained more intensely in S1/S2 segments compared with S3 segment in medullary rays, whereas the S3 segment in the outer stripe remained unstained. Expression of NaDC3, OAT1, OAT2, and OAT3 proteins exhibited considerable interindividual variability in both male and female kidneys, and sex differences in their expression could not be detected. Our experiments provide a side-by-side comparison of basolateral transporters cooperating in renal OA secretion in the human kidney.
Databáze: OpenAIRE
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