In-vivo adaptation of the mouse renal sodium-phosphate transporter to low P i diet is not related to gene transcription

Abstract

Previous studies have demonstrated that dietary phosphate deprivation increases sodium-dependent uptake of phosphate (P i) by renal brush-border membrane vesicles in several mammalian species. These studies demonstrated that the V max of transport was increased without a change in the K m. Subsequently, molecular tools specific for the mouse sodium-phosphate transporter became available, and these were used to show that low P i diet increased functional and immunoreactive transporter protein, and mRNA encoding the transporter in the mouse. These results suggested that increased gene transcription was responsible for these observations. The current investigation was designed to investigate this possibility. Mice were placed on a control P i diet (0.4% P i and 0.45% Ca ++) or a low P i diet (0.02% P i and 0.45% Ca ++) for 7 days, and nuclei were isolated from kidney cortex. Renal sodium-phosphate transporter transcription rates were determined by nuclear run-on assays, and were compared to β-actin and sodium-hydrogen exchanger isoform-1 (NHE-1) relative transcription rates. Results showed similar relative transporter transcription rates in mice on control diet as compared to mice on low P i diet (control diet 1.30 ± 0.11 and low P i diet 1.07 ± 0.21 [normalized for β-actin], and control diet 1.28 ± 0.28 and low P i diet 0.82 ± 0.25 [normalized for NHE-1]). These results suggest that adaptation of the renal Na + P i transporter to dietary phosphate deprivation does not involve gene transcription, but rather is most likely related to mRNA stability or translational efficiency.