Urate transport via human PAH transporter hOAT1 and its gene structure
Autor: | Hitoshi Endou, Yasunori Utsunomiya, Michio Takeda, Kimiyoshi Ichida, Tatsuo Hosoya, Hiroaki Kimura, Makoto Hosoyamada |
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Rok vydání: | 2003 |
Předmět: |
Gout
Organic anion transporter 1 organic anion transporter Sodium Salicylate Blotting Western Organic Anion Transport Protein 1 Kidney Urate transport Cell Line salicylate chemistry.chemical_compound Benzbromarone pyrazine carboxylic acid medicine Humans Carbon Radioisotopes Hyperuricemia Cloning Molecular Gene Library biology Probenecid Anti-Inflammatory Agents Non-Steroidal Biological Transport Transporter Exons Uricosuric Agents medicine.disease Pyrazinamide Protein Structure Tertiary Uric Acid chemistry Biochemistry Nephrology biology.protein urate Uric acid Female Kidney Diseases p-Aminohippuric Acid familial juvenile gouty nephropathy para-aminohippurate |
Zdroj: | Kidney International. 63:143-155 |
ISSN: | 0085-2538 |
Popis: | Urate transport via human PAH transporter hOAT1 and its gene structure.BackgroundWe recently cloned the human organic anion transporter 1 (hOAT1) as a p-aminohippurate (PAH) transporter. Whether urate is transported by the PAH transporter in humans remains unclear. Familial juvenile gouty nephropathy (FJGN) is thought to develop as a result of an abnormality in the urate transporter.MethodsTo determine if hOAT1 transported urate, the cellular uptakes of PAH and urate were determined, as were the inhibition profiles of inorganic anions, and uricosuric and antiuricosuric agents using a mouse S2 cell line expressing hOAT1. The hOAT1 gene was cloned from a genomic library using full-length hOAT1-1 cDNA as a probe. The coding regions of the hOAT1 genes of two sisters with FJGN were sequenced. Also, immunohistochemical fluorescence analysis of hOAT1 in the kidney of the younger sister with FJGN was performed.ResultsThe Km and Vmax values of urate transport via hOAT1 were 943 ± 84 μmol/L and 1286 ± 162 pmol/mg protein/min, respectively. The order of the IC50 of urate transport via hOAT1 was benzbromarone < probenecid < salicylate or pyrazine carboxylic acid. The 10.9 kb hOAT1 gene was found to be interrupted by nine introns. Mutations in the coding region of the hOAT1 gene from the two sisters with FJGN were undetectable. Immunohistochemical fluorescent staining showed that hOAT1 in the kidney of the younger sister was similar to that of control individuals.ConclusionsOur data show that hOAT1 transports urate, and the inhibition profiles of uricosuric and antiuricosuric agents are defined. hOAT1 is not responsible for FJGN in the two sisters examined in this study. |
Databáze: | OpenAIRE |
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