Vascular endothelial growth factor increases the intracellular magnesium.
Vascular endothelial growth factor (VEGF) is one of the key players in the process of angiogenesis. However, its underlying mechanism remains unclear. Mg2+ is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of VEGF on intracellular Mg2+ in human umbilical vein endothelial cells (HUVECs). VEGF-A165 increased the intracellular Mg2+ concentration ([Mg2+]i) in a dose-dependent manner, with or without extracellular Mg2+, and the increase of [Mg2+]i was blocked by pretreatment with SU1498, tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) or phospholipase Cgamma (PLCgamma) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) had no effect on the VEGF-induced [Mg2+]i increase. These results suggest that VEGF-A165 increases the [Mg2+]i from the intracellular Mg2+ stores through the tyrosine kinase/PI3K/PLCgamma-dependent signaling pathways.
Hong
Bing-Zhe
BZ
Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk 560-182, Republic of Korea.
Kang
Hyung-Sub
HS
So
June-No
JN
Kim
Han-Na
HN
Park
Sun-Ah
SA
Kim
Shang-Jin
SJ
Kim
Kyung-Ryoul
KR
Kwak
Yong-Geun
YG
D000730:Androstadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D002934:Cinnamates; D004963:Estrenes; D009025:Morpholines; D010446:Peptide Fragments; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011760:Pyrrolidinones; C483044:SU 1498; D020032:Tyrphostins; D042461:Vascular Endothelial Growth Factor A; C511613:vascular endothelial growth factor A (138-165); 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; D011505:Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D051966:Phospholipase C gamma; D008274:Magnesium; C060641:tyrphostin A23; D000077191:Wortmannin