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.
Ferrelli, F., Pastore, D., Capuani, B., Lombardo, M.F., Blot Chabaud, M., Coppola, A., et al. (2015). Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia. ACTA DIABETOLOGICA, 52(1), 55-64.
|Tipologia:||Articolo su rivista|
|Citazione:||Ferrelli, F., Pastore, D., Capuani, B., Lombardo, M.F., Blot Chabaud, M., Coppola, A., et al. (2015). Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia. ACTA DIABETOLOGICA, 52(1), 55-64.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
Settore MED/09 - Medicina Interna
Settore MED/04 - Patologia Generale
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s00592-014-0600-4|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||feb-2015|
|Titolo:||Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia|
|Autori:||Ferrelli, F; Pastore, D; Capuani, B; Lombardo, MF; Blot Chabaud, M; Coppola, A; Basello, K; Galli, A; Donadel, G; Romano, M; Caratelli, S; Pacifici, F; Arriga, R; Di Daniele, N; Sbraccia, P; Sconocchia, G; Bellia, A; Tesauro, M; Federici, M; Della Morte, D; Lauro, D|
|Appare nelle tipologie:||01 - Articolo su rivista|