title: Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia.
abstract: Diabetic hyperglycaemia causes endothelial dysfunction mainly by impairing endothelial nitric oxide (NO) production. Moreover, hyperglycaemia activates several noxious cellular pathways including apoptosis, increase in reactive oxygen species (ROS) levels and diminishing Na(+)-K(+) ATPase activity which exacerbate vascular damage. Serum glucocorticoid kinase (SGK)-1, a member of the serine/threonine kinases, plays a pivotal role in regulating NO production through inducible NO synthase activation and other cellular mechanisms. Therefore, in this study, we aimed to investigate the protective role of SGK-1 against hyperglycaemia in human umbilical endothelial cells (HUVECs). We used retrovirus to infect HUVECs with either SGK-1, SGK-1Δ60 (lacking of the N-60 amino acids-increase SGK-1 activity) or SGK-1Δ60KD (kinase-dead constructs). We tested our hypothesis in vitro after high glucose and glucosamine incubation. Increase in SGK-1 expression and activity (SGK-1Δ60) resulted in higher production of NO, inhibition of ROS synthesis and lower apoptosis in endothelial cell after either hyperglycaemia or glucosamine treatments. Moreover, in this study, we showed increased GLUT-1 membrane translocation and Na(+)-K(+) ATPase activity in cell infected with SGK-1Δ60 construct. These results suggest that as in endothelial cells, an increased SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated NO production after different noxae stimuli. Therefore, SGK-1 may represent a specific target to further develop novel therapeutic options against diabetic vascular disease.
authors: Laboratory of Molecular Medicine, Department of Systems Medicine, University of Rome Tor Vergata, Montpellier, 1 Street, 00133, Rome, Italy.
authors: Francesca
authors: F
authors: Ferrelli
authors: Donatella
authors: D
authors: Pastore
authors: Barbara
authors: B
authors: Capuani
authors: Marco F
authors: MF
authors: Lombardo
authors: Marcel
authors: M
authors: Blot-Chabaud
authors: Andrea
authors: A
authors: Coppola
authors: Katia
authors: K
authors: Basello
authors: Angelica
authors: A
authors: Galli
authors: Giulia
authors: G
authors: Donadel
authors: Maria
authors: M
authors: Romano
authors: Sara
authors: S
authors: Caratelli
authors: Francesca
authors: F
authors: Pacifici
authors: Roberto
authors: R
authors: Arriga
authors: Nicola
authors: N
authors: Di Daniele
authors: Paolo
authors: P
authors: Sbraccia
authors: Giuseppe
authors: G
authors: Sconocchia
authors: Alfonso
authors: A
authors: Bellia
authors: Manfredi
authors: M
authors: Tesauro
authors: Massimo
authors: M
authors: Federici
authors: David
authors: D
authors: Della-Morte
authors: Davide
authors: D
authors: Lauro
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D005947:Glucose / Q000009:adverse effects / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D005947:Glucose; D017874:Immediate-Early Proteins; D007328:Insulin; D009569:Nitric Oxide; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases