【Background】
Idiopathic Basal Ganglia Calcification (IBGC) is a progressive neurodegenerative disease characterized by calcification of the basal ganglia and cerebellar dentate nucleus. Several gene mutations of IBGC are reported, including SLC20A2 which are involved in phosphate transport. IBGC is thought to be caused by abnormal phosphate transport. However, its mechanism is not yet clear in central nervous system. Therefore, we elucidate the regulation of phosphate transport in neuronal cells, focusing on PDGF-BB, which is one of the causative gene of IBGC and activates phosphate transport in vascular smooth muscle cells.
【Methods】
The effect of PDGF-BB on phosphate uptake was evaluated with SLC20A2-KD (knockdown) SH-SY5Y cells, which is the human neuroblastoma cell type. To determine whether the effect of PDGF-BB is mediated by SLC20A1 or SLC20A2, knockdown assays were conducted. To investigate the mechanism of PDGF-BB on the phosphate uptake, the expression and membrane translocation of phosphate transporters, PiT1 and PiT2 (encoded by SLC20A1 or SLC20A2) was evaluated when PDGF-BB was treated.
【Results】
PDGF-BB enhanced the phosphate uptake by SLC20A1, not SLC20A2. Interestingly, the activation of phosphate uptake by PDGF-BB was not due to increase in the expression of phosphate transporters but to activation of membrane translocation. The activation of membrane translocation by PDGF-BB was canceled when Akt inhibitor was treated.
【Conclusion】
PDGF-BB enhanced the phosphate uptake by the membrane translocation of PiT1, the mechanism of which is thought to be Akt signaling.