Basic fibroblast growth factor increases intracellular magnesium concentration through the specific signaling pathways

Basic fibroblast growth factor (bFGF) plays an important role in angiogenesis. However, the underlying mechanisms are not clear. Mg2+ is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of bFGF on the intracellular Mg2+ concentration ([Mg2+](i)) in human umbilical vein endothelial cells (HUVECs). bFGF increased [Mg2+](i) in a dose-dependent manner, independent of extracellular Mg2+. This bFGF-induced [Mg2+](i) increase was blocked by tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and a phospholipase C gamma (PLC gamma) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) did not affect the bFGF-induced [Mg2+](i) increase. These results suggest that bFGF increases the [Mg2+](i) from the intracellular Mg2+ stores through the tyrosine kinase/PI3K/PLC gamma-dependent signaling pathways.