Demonstration of high-affinity folate binding activity associated with the brush border membranes of rat kidney.

Selhub, Jacob; Rosenberg, Irwin H.

doi:10.1073/pnas.75.7.3090

Cited by 36 publications

(13 citation statements)

References 28 publications

(22 reference statements)

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“…Injection of 3 H-MTHF also confirms the important role of folbp1 for renal tubular reabsorption, showing increased urinary excretion and decreased renal accumulation in folbp1Ϫ/Ϫ. These findings, establishing for the first time in an in vivo model a direct role for folbp1 in epithelia folate uptake, confirms the hypotheses raised by the identification of FR in the kidney proximal tubule and by observations on folate transport in the kidney and in cultured kidney cells (14,20,32,33). In addition, folbp1 is heavily expressed in other absorptive epithelia, including the rodent yolk sac (34) and choroid plexus (15).…”

Section: Discussionsupporting

confidence: 77%

Renal Tubular Reabsorption of Folate Mediated by Folate Binding Protein 1

Birn¹,

Spiegelstein²,

Christensen³

et al. 2005

Journal of the American Society of Nephrology

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Renal tubular reabsorption of filtered folate is essential for the conservation and normal homeostasis of this important vitamin. Different molecular mechanisms have been implicated in epithelial folate transport, including folate receptors. Defective expression or antibody inactivation of these is associated with embryonic defects also correlated with low folate intake; however, their contribution to renal tubular folate reabsorption has not been established. With the use of targeted inactivation of the folate binding protein 1 (folbp1) and folate binding protein 2 (folbp2) genes in mice, the role of folate receptors in renal epithelial folate reabsorption was evaluated during low and normal folate intake. Inactivation of folbp1 was associated with (1) loss of 3 H-folic acid binding to crude kidney membranes, (2) increase in renal folate clearance, and (3) increase in urinary excretion and decrease in renal uptake of injected 3 H-methyltetrahydrofolate. No changes in renal folate handling were observed as a result of folbp2 inactivation. Thus, folbp1 is essential for normal renal tubular folate reabsorption, preventing excessive urinary folate loss. Folbp1 is heavily expressed in choroid plexus, yolk sac, and placenta, supporting a role of folbp1 in folate transport in other tissues. The greatest significance of folbp1 for renal folate uptake was observed at conditions of low folate intake, providing a possible explanation for the ability of folate supplementation to prevent developmental defects associated with folbp1 inactivation.

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Section: Discussionsupporting

confidence: 77%

Renal Tubular Reabsorption of Folate Mediated by Folate Binding Protein 1

Birn¹,

Spiegelstein²,

Christensen³

et al. 2005

Journal of the American Society of Nephrology

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“…This BBM:homogenate ratio for typical BBM enzymes y-glutamyltransferase and maltase was 25.0 and 18.0, respectively; for basolateral plasma membranie marker (Na+-K+) ATPase, the ratio was 0.5; for mitochondrial marker enzymes cytochrome c oxidase and succinate dehydrogenase, the ratio was 0.07 and 0.06, respectively. These results are similar to those obtained by others (18)(19)(20) and indicate high purity of BBM fraction.…”

supporting

confidence: 82%

Renal Adaptation to a Low Phosphate Diet in Rats

Shah¹,

Kempson²,

Northrup³

et al. 1979

J. Clin. Invest.

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A B S T R A C T The major renal adaptive changes in response to selective dietary phosphate restriction are a marked reduction in urinary excretion of phosphate and an increased urinary excretion of calcium; at the cellular level, there is selective increase in renal cortical brush border membrane phosphate uptake and increase in specific activity of alkaline phosphatase. In the present study we examined whether these functional and biochemical adaptive changes could be blocked by drugs known to inhibit protein synthesis.Administration of actinomycin D or cycloheximide to rats switched from a diet with normal phosphate content (0.7%) to a diet with low (0.07%) phosphate content either completely (actinomycin D) or partially (cycloheximide) prevented the expected decrease in urinary excretion of phosphate and increase in the urinary excretion of calcium. The specific activity of alkaline phosphatase measured in crude membrane fraction (washed 100,000 g pellet) from renal cortical homogenate in animals fed a low phosphate diet and treated with actinomycin D or with cycloheximide was significantly lower than in control animals also on a low phosphate diet receiving placebo; but there were no differences between treated and untreated animals in the activities of two other brush border enzymes, y-glutamyltransferase and leucine aminopeptidase. Actinomycin D administered to rats maintained on a normal phosphate diet throughout the course of the experiment caused an increase in the urinary excretion of phosphate on the last (6th) day of the experiment but did not change urinary excretion of calcium. In acute clearance experiments, infusion of actinomycin D to rats adapted to a low phosphate diet did not increase fractional excretion of phosphate.In separate experiments, using the same dietary protocol as above, brush border membrane fraction (vesicles) was prepared from renal cortex of rats sacrificed at the end of the experiment. In this preparation Na+-dependent 32Pi and D-[3H]glucose uptake and activities of brush border enzymes membrane were determined. Brush border membrane vesicles prepared from rats fed a low phosphate diet showed significantly higher Na+-dependent 32Pi uptake compared with rats fed a normal phosphate diet. This increase in -'Pi uptake was completely prevented when rats on a low phosphate diet were simultaneously treated with actinomycin D. These differences were specific for 32Pi transport as no differences were observed in D_[3H]glucose uptake among the three groups. There was a positive correlation (r = 0.82, P < 0.01) between 32Pi uptake and specific activity of alkaline phosphatase measured in aliquots ofthe same brush border membranes, whereas no such correlation was observed with two other brush border membrane enzymes y-glutamyltransferase and leucine aminopeptidase.These observations show that actinomycin D prevents both the functional and cellular renal adaptive changes induced by a low phosphate diet. Taken together, these observations suggest that renal adaptation to a low phosphate ...

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“…Two folate transport proteins have been identified in kidney tissue: the reduced folate carrier (RFC) and the folate receptor (FR) (27,33,49,51). The RFC is found on the basolateral surface of kidney proximal tubule cells (55), while FRs are found on the apical brush-border membrane (3,12,22,24,49).…”

mentioning

confidence: 99%