Cytosolic calcium microdomains by arachidonic acid and nitric oxide in endothelial cells.
Intracellular calcium signals activated by growth factors in endothelial cells during angiogenesis regulate cytosolic and nuclear events involved in survival, proliferation and motility. Among the intracellular messengers released after proangiogenic stimulation (bFGF, VEGF), arachidonic acid (AA), nitric oxide (NO) and their metabolites play a key role and their effects are strictly related to calcium homeostasis. Recently, we showed that AA and NO are able to stimulate the opening of store-independent calcium-permeable channels in the plasmamembrane of bovine aortic endothelial cells (BAECs). Here, we studied the intracellular spatiotemporal dynamics of AA- and NO-induced calcium increases following store-independent calcium entry from extracellular medium. Using confocal calcium imaging, we show that calcium entry is preferentially restricted to peripheral cytosolic microdomains and does not necessarily invade the nuclear region. These results support the existence of local mitogen-activated calcium signals. Several factors could account for this spatial restriction, including the geometry of the cells and the clusterization of calcium channels and other signalling molecules. Intracellular calcium fingerprints could contribute to the specificity of endothelial cell responses to angiogenic factors.
Tomatis
Cristiana
C
Department of Animal and Human Biology, University of Torino, Italy.
Fiorio Pla
Alessandra
A
Munaron
Luca
L
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*
D045462:Endothelium-Dependent Relaxing Factors; D016718:Arachidonic Acid; D009569:Nitric Oxide; D002118:Calcium