Noncrystalline uric acid inhibits proteoglycan and glycosaminoglycan synthesis in distal tubular epithelial cells (MDCK)

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dc.contributor.authorBorges, Fernanda Teixeira [UNIFESP]
dc.contributor.authorDalboni, Maria Aparecida [UNIFESP]
dc.contributor.authorMichelacci, Yara Maria [UNIFESP]
dc.contributor.authorSchor, Nestor [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2015-06-14T13:41:54Z
dc.date.available2015-06-14T13:41:54Z
dc.date.issued2010-10-01
dc.description.abstractHyperuricemia is associated with renal stones, not only consisting of uric acid (UrAc) but also of calcium oxalate (CaOx). Glycosaminoglycans (GAGs) are well-known inhibitors of growth and aggregation of CaOx crystals. We analyzed the effect of noncrystalline UrAc on GAG synthesis in tubular distal cells. MDCK (Madin-Darby canine kidney) cells were exposed to noncrystalline UrAc (80 µg/mL) for 24 h. GAGs were labeled metabolically and characterized by agarose gel electrophoresis. The expression of proteoglycans and cyclooxygenase 2 (COX-2) was assessed by real-time PCR. Necrosis, apoptosis and prostaglandin E2 (PGE2) were determined by acridine orange, HOESCHT 33346, and ELISA, respectively. CaOx crystal endocytosis was evaluated by flow cytometry. Noncrystalline UrAc significantly decreased the synthesis and secretion of heparan sulfate into the culture medium (UrAc: 2127 ± 377; control: 4447 ± 730 cpm) and decreased the expression of perlecan core protein (UrAc: 0.61 ± 0.13; control: 1.07 ± 0.16 arbitrary units), but not versican. Noncrystalline UrAc did not induce necrosis or apoptosis, but significantly increased COX-2 and PGE2 production. The effects of noncrystalline UrAc on GAG synthesis could not be attributed to inflammatory actions because lipopolysaccharide, as the positive control, did not have the same effect. CaOx was significantly endocytosed by MDCK cells, but this endocytosis was inhibited by exposure to noncrystalline UrAc (control: 674.6 ± 4.6, CaOx: 724.2 ± 4.2, and UrAc + CaOx: 688.6 ± 5.4 geometric mean), perhaps allowing interaction with CaOx crystals. Our results indicate that UrAc decreases GAG synthesis in MDCK cells and this effect could be related to the formation of UrAc and CaOx stones.en
dc.description.affiliationUniversidade Federal de São Paulo (UNIFESP) Departamento de Medicina Disciplina de Nefrologia
dc.description.affiliationUniversidade Federal de São Paulo (UNIFESP) Departamento de Bioquímica Disciplina de Biologia Molecular
dc.description.affiliationUnifespUNIFESP, Depto. de Medicina Disciplina de Nefrologia
dc.description.affiliationUnifespUNIFESP, Depto. de Bioquímica Disciplina de Biologia Molecular
dc.description.sourceSciELO
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFINEP
dc.description.sponsorshipFundacao Oswaldo Ramos (FOR)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent957-963
dc.identifierhttp://dx.doi.org/10.1590/S0100-879X2010007500095
dc.identifier.citationBrazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 43, n. 10, p. 957-963, 2010.
dc.identifier.doi10.1590/S0100-879X2010007500095
dc.identifier.fileS0100-879X2010001000006.pdf
dc.identifier.issn0100-879X
dc.identifier.scieloS0100-879X2010001000006
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/5951
dc.identifier.wosWOS:000283263500006
dc.language.isoeng
dc.publisherAssociação Brasileira de Divulgação Científica
dc.relation.ispartofBrazilian Journal of Medical and Biological Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectNoncrystalline uric aciden
dc.subjectGlycosaminoglycanen
dc.subjectMDCKen
dc.subjectLipopolysaccharideen
dc.subjectApoptosisen
dc.subjectProteoglycanen
dc.titleNoncrystalline uric acid inhibits proteoglycan and glycosaminoglycan synthesis in distal tubular epithelial cells (MDCK)en
dc.typeinfo:eu-repo/semantics/article
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