NDLI: Angiogenesis: role of calcium-mediated signal transduction.

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Theoretical predictions of folding pathways by using the proximity rule, with applications to bovine pancreatic trypsin inhibitor.

Angiogenesis: role of calcium-mediated signal transduction.

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Angiogenesis: role of calcium-mediated signal transduction.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kohn, E. C. Wersto, R. P. Liotta, L. A. Alessandro, R. Spoonster, J.
Description	Author Affiliation: Kohn EC ( Signal Transduction and Prevention Unit, National Cancer Institute, Bethesda, MD 20892.);
Abstract	During angiogenesis, endothelial cells react to stimulation with finely tuned signaling responses. The role of calcium-regulated signaling in angiogenesis has not been defined. This study investigated the calcium dependency of endothelial cell proliferation and invasion by using an inhibitor of ligand-stimulated calcium influx, CAI (carboxy-amidotriazole). Incubation with CAI significantly inhibited proliferation of human umbilical vein endothelial cells (HUVECs) in response to serum (IC50 = 1 microM) or basic fibroblast growth factor (FGF2; P2 < 0.005 at 10 microM). Statistically significant inhibition of HUVEC adhesion and motility to basement membrane proteins laminin, fibronectin, and type IV collagen was demonstrated (adhesion, P2 < 0.004-0.01; motility, P2 < 0.009-0.018). Marked inhibition of native and FGF2-induced gelatinase activity was shown by zymogram analysis and was confirmed by Northern blot analysis. CAI inhibited HUVEC tube formation on Matrigel and inhibited in vivo angiogenesis in the chicken chorioallantoic membrane assay, 67% at 20 microM and 56% at 10 microM compared with 16% for an inactive CAI analog or 9% for 0.1% dimethyl sulfoxide control. Incubation of HUVECs with CAI and/or FGF2 followed by immunoprecipitation with anti-phosphotyrosine antibody showed inhibition of FGF2-induced tyrosine phosphorylation of proteins in the range 110-150 kDa. These results suggest that calcium-regulated events are important in native and FGF2-stimulated HUVEC proliferation and invasion, perhaps through regulation of FGF2-induced phosphorylation events, and indicate a role for calcium in the regulation of angiogenesis in vivo.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	92
Language	English
Publisher	National Academy of Sciences
Publisher Date	1995-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Calcium Physiology Endothelium, Vascular Neovascularization, Pathologic Triazoles Aminoimidazole Carboxamide Analogs & Derivatives Pharmacology Calcium Channel Blockers Cell Adhesion Cell Division Cell Movement Cells, Cultured Collagen Drug Combinations Cytology Extracellular Matrix Proteins Fibroblast Growth Factor 2 Gelatinases Metabolism In Vitro Techniques Laminin Matrix Metalloproteinase 2 Metalloendopeptidases Phosphotyrosine Proteoglycans Signal Transduction Tyrosine Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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