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Burckhardt, Birgitta Christina; Brzica, Hrvoje; Breljak, Davorka; Vrhovac, Ivana; Micek, Vedran; Lovric, Mila; Schnedler, Nina; Burckhardt, Gerhard
The FASEB journal, 04/2012, Letnik: 26, Številka: S1Journal Article
Abstract only The epidemiological incidence of oxalate (OX) nephrolithiasis is higher in men than in women. More than 85% of the body OX is produced in liver and then released into the systemic circulation by the action of sulfate‐OX exchanger sat1 in the hepatocyte sinusoidal membrane. In kidneys, sat1 in the proximal tubule basolateral membrane mediates OX uptake, whereas the chloride‐formate‐ oxalate exchanger CFEX in the brush‐border membrane finally extrudes OX into the urine. Here we used the model of ethylene glycol (EG)‐induced OX nephrolithiasis in adult male (M) and female (F) rats to study sat1, CFEX, and rate‐limiting enzymes of OX synthesis, alcohol dehydrogenase (Adh1) and hydroxy acid oxidase (Hao1). Compared to controls, EG‐treated animals exhibited higher concentrations of OX in plasma and urine and higher abundance of OX crystals in urine, with a M dominance. Sat1 protein in liver and kidneys, which was M‐dominant in control animals, in EG‐treated animals increased only in F rats, while sat1 mRNA stayed unchanged. CFEX mRNA in both organs was sex‐independent and unaffected by EG treatment. Adh1 and Hao1 mRNA in both organs remained also unchanged upon EG treatment. In conclusion, despite hyperoxaluria in EG‐treated animals, the expression of sat1 in M and of CFEX in both sexes was sufficient to handle the EG‐induced production and secretion of OX.
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