Glyoxylate is a substrate of the sulfate-oxalate exchanger, sat-1, and increases its expression in HepG2 cells.
BACKGROUND & AIMS: Hyperoxaluria is a major problem causing nephrolithiasis. Little is known about the regulation of oxalate transport from the liver, the main organ for oxalate synthesis, into the circulation. Since the sulfate anion transporter-1(sat-1) is present in the sinusoidal membrane of hepatocytes and translocates oxalate, its impact on increased oxalate synthesis was studied. METHODS: Sat-1 expressing oocytes were used for cis-inhibition, trans-stimulation, and efflux experiments with labelled sulfate and oxalate to demonstrate the interactions of oxalate, glyoxylate, and glycolate with sat-1. HepG2 cells were incubated with oxalate and its precursors (glycine, hydroxyproline, glyoxylate, and glycolate). Changes in endogenous sat-1 mRNA-expression were examined using real-time PCR. After incubation of HepG2 cells in glyoxylate, sat-1 protein-expression was analysed by Western blotting, and sulfate uptake into HepG2 cells was measured. RT-PCR was used to screen for mRNA of other transporters. RESULTS: While oxalate and glyoxylate inhibited sulfate uptake, glycolate did not. Sulfate and oxalate uptake were trans-stimulated by glyoxylate but not by glycolate. Glyoxylate enhanced sulfate efflux. Glyoxylate was the only oxalate precursor stimulating sat-1 mRNA-expression. After incubation of HepG2 cells in glyoxylate, both sat-1 protein-expression and sulfate uptake into the cells increased. mRNA-expression of other transporters in HepG2 cells was not affected by glyoxylate treatment. CONCLUSIONS: The oxalate precursor glyoxylate was identified as a substrate of sat-1. Upregulated expression of sat-1 mRNA and of a functional sat-1 protein indicates that glyoxylate may be responsible for the elevated oxalate release from hepatocytes observed in hyperoxaluria.[1]References
- Glyoxylate is a substrate of the sulfate-oxalate exchanger, sat-1, and increases its expression in HepG2 cells. Schnedler, N., Burckhardt, G., Burckhardt, B.C. J. Hepatol. (2011) [Pubmed]
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