title: Basal nitric oxide release attenuates cell migration of HeLa and endothelial cells.
abstract: Nitric oxide (NO) generated by endothelial NO synthase (eNOS) is a key regulator of endothelial cell (EC) migration. Whereas the effects of acute NO generation are generally stimulatory, the role of chronic basal NO release has not been explored so far. Here, we addressed this question both in HeLa and in human endothelial cells. In stably transfected HeLa cells, inducibly expressing eNOS, expression of the enzyme per se blunted the phosphorylation of Akt/PKB in response to serum and strongly inhibited chemotaxis, an effect partially blocked by eNOS- and soluble guanylyl cyclase (sGC) inhibitors. Likewise, long-term pre-treatment of non-transfected HeLa cells with nanomolar concentrations of an NO donor inhibited subsequent migration, an effect blocked by sGC inhibition and mimicked by a cGMP analog. Finally, EC migration was stimulated by chronic pre-treatment with an eNOS inhibitor. Thus, in addition to its well-known stimulatory role, eNOS attenuates migration through basal long-term NO release.
authors: Department of Pharmaco-Biological Science, University of Catanzaro Magna Graecia, Catanzaro, Italy.
authors: Stefania
authors: S
authors: Bulotta
authors: Maria Vincenza
authors: MV
authors: Ierardi
authors: Jessica
authors: J
authors: Maiuolo
authors: Maria Grazia
authors: MG
authors: Cattaneo
authors: Andrea
authors: A
authors: Cerullo
authors: Lucia M
authors: LM
authors: Vicentini
authors: Nica
authors: N
authors: Borgese
mesh_terms: D002465:Cell Movement; D002633:Chemotaxis; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt