Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Am J Physiol Renal Physiol
2016 Jan 15;3102:F152-9. doi: 10.1152/ajprenal.00406.2015.
Show Gene links
Show Anatomy links
Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6)-dependent mechanism in an insect model of calcium oxalate nephrolithiasis.
Landry GM
,
Hirata T
,
Anderson JB
,
Cabrero P
,
Gallo CJ
,
Dow JA
,
Romero MF
.
???displayArticle.abstract???
Nephrolithiasis is one of the most common urinary tract disorders, with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dPrestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus laevis oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to Malpighian tubules ex vivo. Neither compound affected CaOx crystallization in dPrestin knockdown animals, indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore, thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared with oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization.
Agroyannis,
Sodium thiosulphate in the treatment of renal tubular acidosis I with nephrocalcinosis.
1994, Pubmed
Agroyannis,
Sodium thiosulphate in the treatment of renal tubular acidosis I with nephrocalcinosis.
1994,
Pubmed
Asplin,
Thiosulfate reduces calcium phosphate nephrolithiasis.
2009,
Pubmed
Chen,
Ethylene glycol induces calcium oxalate crystal deposition in Malpighian tubules: a Drosophila model for nephrolithiasis/urolithiasis.
2011,
Pubmed
Clark,
Species differences in Cl- affinity and in electrogenicity of SLC26A6-mediated oxalate/Cl- exchange correlate with the distinct human and mouse susceptibilities to nephrolithiasis.
2008,
Pubmed
,
Xenbase
Dow,
Drosophila provides rapid modeling of renal development, function, and disease.
2010,
Pubmed
Freel,
Ileal oxalate absorption and urinary oxalate excretion are enhanced in Slc26a6 null mice.
2006,
Pubmed
Hirata,
Ion and solute transport by Prestin in Drosophila and Anopheles.
2012,
Pubmed
,
Xenbase
Hirata,
In vivo Drosophilia genetic model for calcium oxalate nephrolithiasis.
2012,
Pubmed
Jiang,
Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.
2006,
Pubmed
Jiang,
Specificity of anion exchange mediated by mouse Slc26a6.
2002,
Pubmed
,
Xenbase
Kato,
Identification of renal transporters involved in sulfate excretion in marine teleost fish.
2009,
Pubmed
,
Xenbase
Kurita,
Identification of intestinal bicarbonate transporters involved in formation of carbonate precipitates to stimulate water absorption in marine teleost fish.
2008,
Pubmed
,
Xenbase
Miller,
Drosophila melanogaster as an emerging translational model of human nephrolithiasis.
2013,
Pubmed
Monico,
Phenotypic and functional analysis of human SLC26A6 variants in patients with familial hyperoxaluria and calcium oxalate nephrolithiasis.
2008,
Pubmed
,
Xenbase
Okonkwo,
A pilot study of the effect of sodium thiosulfate on urinary lithogenicity and associated metabolic acid load in non-stone formers and stone formers with hypercalciuria.
2013,
Pubmed
Plata,
Zebrafish Slc5a12 encodes an electroneutral sodium monocarboxylate transporter (SMCTn). A comparison with the electrogenic SMCT (SMCTe/Slc5a8).
2007,
Pubmed
,
Xenbase
Rodgers,
Sulfate but not thiosulfate reduces calculated and measured urinary ionized calcium and supersaturation: implications for the treatment of calcium renal stones.
2014,
Pubmed
Romero,
Cloning and functional expression of rNBC, an electrogenic Na(+)-HCO3- cotransporter from rat kidney.
1998,
Pubmed
,
Xenbase
Sciortino,
Cation and voltage dependence of rat kidney electrogenic Na(+)-HCO(-)(3) cotransporter, rkNBC, expressed in oocytes.
1999,
Pubmed
,
Xenbase
Wang,
Renal and intestinal transport defects in Slc26a6-null mice.
2005,
Pubmed
Weber,
Expression of prestin-homologous solute carrier (SLC26) in auditory organs of nonmammalian vertebrates and insects.
2003,
Pubmed
Xie,
Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1.
2002,
Pubmed
,
Xenbase
Yatzidis,
Treatment of chronic renal failure with dietary fiber.
1985,
Pubmed
Yatzidis,
Successful sodium thiosulphate treatment for recurrent calcium urolithiasis.
1985,
Pubmed
