Sat1 is dispensable for active oxalate secretion in mouse duodenum

Ko, Narae; Knauf, Felix; Jiang, Zhong‐Xing; Markovich, Daniel; Aronson, Peter S.

doi:10.1152/ajpcell.00385.2011

Cited by 23 publications

(23 citation statements)

References 21 publications

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“…Recent development and study of the SAT1-KO mouse implied there was diminished intestinal oxalate secretion in the absence of SAT1, contributing to higher rates of oxalate absorption, causing hyperoxaluria, hyperoxalemia and nephrolithiasis in these animals [19]. With SAT1 present throughout the small intestine [19, 43, 44], this opened up the exciting possibility that it might be functioning in series with apical PAT1 to mediate transcellular oxalate secretion [19], a prospect explored by Ko et al [44]. However, they were forced to concede that SAT1 was “dispensable for active oxalate secretion”, at least in the duodenum.…”

Section: The Pathways and Mechanisms For Oxalate Transport Across Thementioning

confidence: 99%

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

Whittamore

Hatch

2016

Urolithiasis

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The intestine exerts a considerable influence over urinary oxalate in two ways, through the absorption of dietary oxalate and by serving as an adaptive extra-renal pathway for elimination of this waste metabolite. Knowledge of the mechanisms responsible for oxalate absorption and secretion by the intestine therefore have significant implications for understanding the etiology of hyperoxaluria, as well as offering potential targets for future treatment strategies for calcium oxalate kidney stone disease. In this review, we present the recent developments and advances in this area over the past 10 years, and put to the test some of the new ideas that have emerged during this time, using human and mouse models. A key focus for our discussion are the membrane-bound anion exchangers, belonging to the SLC26 gene family, some of which have been shown to participate in transcellular oxalate absorption and secretion. This has offered the opportunity to not only examine the roles of these specific transporters, revealing their importance to oxalate homeostasis, but to also probe the relative contributions made by the active transcellular and passive paracellular components of oxalate transport across the intestine. We also discuss some of the various physiological stimuli and signaling pathways which have been suggested to participate in the adaptation and regulation of intestinal oxalate transport. Finally, we offer an update on research into Oxalobacter formigenes, alongside recent investigations of other oxalate-degrading gut bacteria, in both laboratory animals and humans.

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Section: The Pathways and Mechanisms For Oxalate Transport Across Thementioning

confidence: 99%

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

Whittamore

Hatch

2016

Urolithiasis

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“…Furthermore, a recent study on mouse duodenum by Ko et al (120) questioned the role of Sat-1 in transporting oxalate, since the active oxalate secretion in this intestinal segment was not reduced in Sat1 KO mice. Another transporter from the same family is the protein known as "Down-Regulated in Adenoma" [DRA (SLC26A3)/Dra (Slc26a3)], which mediates Na + -independent SO 4 2-and oxalate uptake in mouse intestine (121).…”

Section: Oxalate-handling Transporters and Their Role In Hyperoxalurimentioning

confidence: 99%

Oxalate: From the Environment to Kidney Stones

Brzica

Breljak

Burckhardt

et al. 2013

Archives of Industrial Hygiene and Toxicology

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Oxalate urolithiasis (nephrolithiasis) is the most frequent type of kidney stone disease. Epidemiological research has shown that urolithiasis is approximately twice as common in men as in women, but the underlying mechanism of this sex-related prevalence is unclear. Oxalate in the organism partially originate from food (exogenous oxalate) and largely as a metabolic end-product from numerous precursors generated mainly in the liver (endogenous oxalate). Oxalate concentrations in plasma and urine can be modifi ed by various foodstuffs, which can interact in positively or negatively by affecting oxalate absorption, excretion, and/or its metabolic pathways. Oxalate is mostly removed from blood by kidneys and partially via bile and intestinal excretion. In the kidneys, after reaching certain conditions, such as high tubular concentration and damaged integrity of the tubule epithelium, oxalate can precipitate and initiate the formation of stones. Recent studies have indicated the importance of the SoLute Carrier 26 (SLC26) family of membrane transporters for handling oxalate. Two members of this family [Sulfate Anion Transporter 1 (SAT-1; SLC26A1) and Chloride/Formate EXchanger (CFEX; SLC26A6)] may contribute to oxalate transport in the intestine, liver, and kidneys. Malfunction or absence of SAT-1 or CFEX has been associated with hyperoxaluria and urolithiasis. However, numerous questions regarding their roles in oxalate transport in the respective organs and male-prevalent urolithiasis, as well as the role of sex hormones in the expression of these transporters at the level of mRNA and protein, still remain to be answered.

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“…The macroscopically unidirectional transport may reflect a very low affinity of SLC26A1 for intracellular oxalate, or much higher affinities for other coextant substrate anions at the intracellular substrate binding site. However, such a system is not active throughout the gut, as evidenced by normal ex vivo oxalate secretion rates by the isolated SLC26A1 −/− mouse duodenum [39]. …”

Section: Discussionmentioning

confidence: 99%

“…However, oxalate secretion by isolated Slc26a1 −/− duodenum was unchanged [39], and Slc26a1 mRNA and protein abundance was unaltered in mice with hyperoxaluria of other causes, questioning the physiological role of SLC26A1 in hyperoxaluria (at least in duodenum) [23]. Human diseases caused by SLC26A1 mutations have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Cl− regulates human SO4 2−/anion exchanger SLC26A1 by altering pH sensitivity of anion transport

Heneghan

Vandorpe

et al. 2016

Pflugers Arch - Eur J Physiol

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Genetic deficiency of the SLC26A1 anion exchanger in mice is known to be associated with hyposulfatemia and hyperoxaluria with nephrolithiasis, but many aspects of human SLC26A1 function remain to be explored. We report here the functional characterization of human SLC26A1, a DIDS-sensitive, electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, bicarbonate, thiosulfate and (with divergent properties) chloride. Human SLC26A1-mediated anion exchange differs from that of its rodent orthologs in its stimulation by alkaline pHo and inhibition by acidic pHo but not pHi, and in its failure to transport glyoxylate. SLC26A1-mediated transport of sulfate and oxalate is highly dependent on allosteric activation by extracellular chloride or nonsubstrate anions. Extracellular chloride stimulates apparent Vmax of human SLC26A1-mediated sulfate uptake by conferring a two-log decrease in sensitivity to inhibition by extracellular protons, without changing transporter affinity for extracellular sulfate. In contrast to SLC26A1-mediated sulfate transport, SLC26A1-associated chloride transport is activated by acid pHo, shows reduced sensitivity to DIDS, and exhibits cation-dependence of its DIDS-insensitive component. Human SLC26A1 resembles SLC26 paralogs in its inhibition by phorbol ester activation of PKC, which differs in its undiminished polypeptide abundance at or near the oocyte surface. Mutation of SLC26A1 residues corresponding to candidate anion binding site-associated residues in avian SLC26A5/prestin altered anion transport in patterns resembling those of prestin. However, rare SLC26A1 polymorphic variants from a patient with renal Fanconi Syndrome and from a patient with nephrolithiasis/calcinosis exhibited no loss-of-function phenotypes consistent with disease pathogenesis.

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Sat1 is dispensable for active oxalate secretion in mouse duodenum

Abstract: PS. Sat1 is dispensable for active oxalate secretion in mouse duodenum.

Cited by 23 publications

References 21 publications

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

The role of intestinal oxalate transport in hyperoxaluria and the formation of kidney stones in animals and man

Oxalate: From the Environment to Kidney Stones

Extracellular Cl− regulates human SO4 2−/anion exchanger SLC26A1 by altering pH sensitivity of anion transport

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