title: NAP reduces murine microvascular endothelial cells proliferation induced by hyperglycemia.
abstract: Hyperglycemia has been identified as a risk factor responsible for micro- and macrovascular complications in diabetes. NAP (Davunetide) is a peptide whose neuroprotective actions are widely demonstrated, although its biological role on endothelial dysfunctions induced by hyperglycemia remains uninvestigated. In the present study we hypothesized that NAP could play a protective role on hyperglycemia-induced endothelial cell proliferation. To this end we investigated the effects of NAP on an in vitro model of murine microvascular endothelial cells grown in high glucose for 7 days. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and cyclin D1 protein expression analysis revealed that NAP treatment significantly reduces viability and proliferation of the cells. Hyperglycemia induced the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase and/or phosphatidylinositol-3 kinase/Akt pathways in a time-dependent manner. NAP treatment reduced the phosphorylation levels of ERK and AKT in cells grown in high glucose. These evidences suggest that NAP might be effective in the regulation of endothelial dysfunction induced by hyperglycemia.
authors.affiliation: Department of Bio-Medical Sciences, Section of Anatomy and Histology, University of Catania, Via S. Sofia, 87, 95123, Catania, Italy.
authors.forename: Agata Grazia
authors.initials: AG
authors.lastname: D'Amico
authors.forename: Soraya
authors.initials: S
authors.lastname: Scuderi
authors.forename: Grazia
authors.initials: G
authors.lastname: Maugeri
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cavallaro
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C425904:davunetide; D005947:Glucose