Phosphate as a novel signal in the intracellular signal transduction

Abstract

The phosphate (Pi)-mediated signal transduction pathways in renal proximal tubular cells and endothelial cells were examined, because Pi depletion and overloading are known to influence gene expression and cellular function. In renal proximal tubular calls (LLC-PK1), Pi depletion resulted in increases in intracellular inositol triphosphate (IP3) and calcium ion (Ca^<2+>) levels, the latter of which may be associated with the maintenance of Pi homeostasis. On the other hand, exposing bovine aortic endothelial cells to excessive Pi load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Pi loading in rat aortic rings inhibited endothelium-dependent vasodilation. A high dietary Pi load in human subjects increased serum Pi level at 2 h and significantly decreased flow-mediated dilation. Thus, it was found that the function of endothelial cells was damaged by the high dietary Pi loading. Taken together, these findings suggest that the changes in serum Pi level are associated with human health by affecting the intracellular Pi signal transduction pathway.