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. Mg(2+) 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 Mg(2+) concentration ([Mg(2+)](i)) in human umbilical vein endothelial cells (HUVECs). bFGF increased [Mg(2+)](i) in a dose-dependent manner, independent of extracellular Mg(2+). This bFGF-induced [Mg(2+)](i) increase was blocked by tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and a phospholipase Cgamma (PLCgamma) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) did not affect the bFGF-induced [Mg(2+)](i) increase. These results suggest that bFGF increases the [Mg(2+)](i) from the intracellular Mg(2+) stores through the tyrosine kinase/PI3K/PLCgamma-dependent signaling pathways.
Hong
Bing-Zhe
BZ
Department of Pharmacology, Chonbuk National University Medical School, Jeonju 560-182, Korea.
Park
Sun-Ah
SA
Kim
Han-Na
HN
Ma
Tian-Ze
TZ
Kim
Han-Gyu
HG
Kang
Hyung-Sub
HS
Kim
Hwan-Gyu
HG
Kwak
Yong-Geun
YG
D000730:Androstadienes / Q000494:pharmacology; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008856:Microscopy, Fluorescence / Q000379:methods; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D020032:Tyrphostins / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D004963:Estrenes; D016222:Fibroblast Growth Factor 2; D005419:Flavonoids; D019833:Genistein; D007093:Imidazoles; D008274:Magnesium; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D011725:Pyridines; D011760:Pyrrolidinones; D020032:Tyrphostins; D000077191:Wortmannin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C060641:tyrphostin A23; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one