Vascular endothelial growth factor increases the intracellular magnesium

Hong, Bing-Zhe; Kang, Hyung-Sub; So, June-No; Kim, Hanna; Park, Sunah; Kim, Shang-Jin; Kwak, Yong-Geun

doi:10.1016/j.bbrc.2006.06.125

Cited by 13 publications

(9 citation statements)

References 42 publications

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“…It is well known that the total concentration of Mg increases throughout the G1 and S phase of the cell cycle [6]. In endothelial cells, growth induced by basic FGF [25] and VEGF [26] is associated with the increase of intracellular Mg concentrations. Recently, TRPM7, which supports multiple cellular and physiologic function including cell viability and growth, has been shown to ensure a rapid Mg influx during the G1 phase of the cell cycle [15].…”

Section: Discussionmentioning

confidence: 99%

Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells

Baldoli¹,

Maier²

2011

Angiogenesis

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Evidence has accumulated to suggest that magnesium might play a role in controlling angiogenesis. Since microvascular endothelial cells are protagonists in this process, we investigated the behavior of these cells cultured in low extracellular magnesium or silenced for its transporter Transient Receptor Potential Melastatin (TRPM)7, essential for cellular magnesium homeostasis. In particular, we focused on some crucial steps of the angiogenic process, i.e. proliferation, migration, protease production and organization in tridimensional structures. Silencing TRPM7 mimics the effects of low extracellular magnesium on human microvascular endothelial cells (HMEC). Indeed, while no effects were observed on the production of metalloproteases and on tridimensional organization on matrigel, both magnesium deficiency and silencing of TRPM7 impair cell migration and inhibit growth by arresting the cells in the G0/G1 and G2/M phases of the cell cycle. Since low extracellular magnesium markedly decreases TRPM7 in HMEC, we suggest that TRPM7 downregulation might mediate low magnesium-induced inhibition of cell growth and migration. Human endothelial cells from the umbilical vein are growth inhibited by low magnesium and growth stimulated after TRPM7 silencing. An impairment of ERK phosphorylation in HMEC silencing TRPM7 is responsible, in part, for the different proliferative behavior of these two cell types. We broadened our studies also to endothelial colony-forming cells and found that they are sensitive to fluctuations of the concentrations of extracellular magnesium, while their proliferation rate is not modulated by TRPM7 silencing. Our results point to magnesium and TRPM7 as a modulators of the angiogenic phenotype of microvascular endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells

Baldoli¹,

Maier²

2011

Angiogenesis

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“…Thus, Mg 2+ chemotaxis involved second messengers and was not due solely to a gradient of integrin-mediated adhesion. Studies of free cytoplasmic Mg 2+ with mag-fura-2 showed that cytoplasmic Mg 2+ rapidly increased in endothelial cells from basal levels of 0.5 mM to 1.1–1.2 mM upon stimulation with the chemoattractants VEGF [95] or bFGF [96] due to release from intracellular stores. While this study does not directly address cellular Mg 2+ levels, our findings point to direct participation of Mg 2+ in the motility process.…”

Section: Discussionmentioning

confidence: 99%

Actin Filament Attachments for Sustained Motility In Vitro Are Maintained by Filament Bundling

Kuhn

2012

PLoS ONE

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We reconstructed cellular motility in vitro from individual proteins to investigate how actin filaments are organized at the leading edge. Using total internal reflection fluorescence microscopy of actin filaments, we tested how profilin, Arp2/3, and capping protein (CP) function together to propel thin glass nanofibers or beads coated with N-WASP WCA domains. Thin nanofibers produced wide comet tails that showed more structural variation in actin filament organization than did bead substrates. During sustained motility, physiological concentrations of Mg2+ generated actin filament bundles that processively attached to the nanofiber. Reduction of total Mg2+ abolished particle motility and actin attachment to the particle surface without affecting actin polymerization, Arp2/3 nucleation, or filament capping. Analysis of similar motility of microspheres showed that loss of filament bundling did not affect actin shell formation or symmetry breaking but eliminated sustained attachments between the comet tail and the particle surface. Addition of Mg2+, Lys-Lys2+, or fascin restored both comet tail attachment and sustained particle motility in low Mg2+ buffers. TIRF microscopic analysis of filaments captured by WCA-coated beads in the absence of Arp2/3, profilin, and CP showed that filament bundling by polycation or fascin addition increased barbed end capture by WCA domains. We propose a model in which CP directs barbed ends toward the leading edge and polycation-induced filament bundling sustains processive barbed end attachment to the leading edge.

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“…For example, we previously observed similar effects in A549 cells [8], and other studies in lung epithelial cells have typically employed U73122 concentrations of at least 10 μM [31,32,33,34]. In endothelial cells, a variety of events mediated by phospholipase C have been shown to be inhibited by 1 μM U73122 [35,36,37,38]. A second difference in the response of the different cell types was the increase in CINC-1 expression following treatment of endothelial cells with 1 μM manumycin A that was not observed in SAECs (Figure 5).…”

Section: Discussionmentioning

confidence: 62%

Common Pathways for Activation of Proinflammatory Gene Expression by G Protein–coupled Receptors in Primary Lung Epithelial and Endothelial Cells

Chang

Chen

Schlueter

et al. 2009

Experimental Lung Research

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Acute lung injury is associated with an inflammatory response resulting from the action of multiple mediators. Many proinflammatory mediators released during lung injury exert effects by binding to G protein-coupled receptors (GPCRs). Our earlier studies showed that substance P (SP), a ligand for the tachykinin 1 receptor, induced NF-κB activation and IL-8 upregulation through a Gq-dependent pathway. Here we extend these findings by examining effects of multiple ligands for Gq-coupled GPCRs in primary human small airway epithelial cells (SAECs) and rat lung microvessel endothelial cells (RLMVECs). SP, bradykinin, protease activated receptor 2 agonist, and platelet activating factor (PAF) stimulated IL-8 production in SAECs, whereas only SP and PAF upregulated CINC-1 (a rat IL-8 homolog) in RLMVECs. Using signaling inhibitors, we investigated PAF-induced IL-8 expression and SP-induced CINC-1 expression in primary cells. Signaling cascades were similar in SAECs and RLMVECs and involved phospholipase C/calcium/PKC and Ras/Raf/Erk pathways. In addition, the tyrosine kinase inhibitor AG 17 and the proteasome inhibitor MG132 significantly reduced IL-8 and CINC-1 expression induced by GPCR ligands. The results demonstrate a common signaling pathway in primary lung epithelial and endothelial cells, suggesting a generalized mechanism for the induction of proinflammatory gene expression by Gq-coupled GPCRs following lung injury.

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Vascular endothelial growth factor increases the intracellular magnesium

Cited by 13 publications

References 42 publications

Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells

Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells

Actin Filament Attachments for Sustained Motility In Vitro Are Maintained by Filament Bundling

Common Pathways for Activation of Proinflammatory Gene Expression by G Protein–coupled Receptors in Primary Lung Epithelial and Endothelial Cells

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