title: Vascular endothelial growth factor increases the intracellular magnesium.
abstract: 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.
authors.affiliation: Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk 560-182, Republic of Korea.
authors.forename: Bing-Zhe
authors.initials: BZ
authors.lastname: Hong
authors.forename: Hyung-Sub
authors.initials: HS
authors.lastname: Kang
authors.forename: June-No
authors.initials: JN
authors.lastname: So
authors.forename: Han-Na
authors.initials: HN
authors.lastname: Kim
authors.forename: Sun-Ah
authors.initials: SA
authors.lastname: Park
authors.forename: Shang-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kyung-Ryoul
authors.initials: KR
authors.lastname: Kim
authors.forename: Yong-Geun
authors.initials: YG
authors.lastname: Kwak
mesh_terms: 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
chemical_list: 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