1. Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia
- Author
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David Della-Morte, Donatella Pastore, Alfonso Bellia, Francesca Ferrelli, Roberto Arriga, Massimo Federici, Marco F. Lombardo, Giuseppe Sconocchia, Barbara Capuani, Giulia Donadel, Davide Lauro, Sara Caratelli, Manfredi Tesauro, Paolo Sbraccia, Maria Romano, Katia Basello, Angelica Galli, Nicola Di Daniele, Andrea Coppola, Francesca Pacifici, and Marcel Blot-Chabaud
- Subjects
medicine.medical_specialty ,Settore MED/09 - Medicina Interna ,Endocrinology, Diabetes and Metabolism ,Apoptosis ,Protein Serine-Threonine Kinases ,Biology ,Nitric Oxide ,medicine.disease_cause ,endothelial dysfunction ,Immediate early protein ,Cell Line ,Immediate-Early Proteins ,Settore MED/13 - Endocrinologia ,Nitric oxide ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,Human Umbilical Vein Endothelial Cells ,Internal Medicine ,medicine ,Humans ,Insulin ,oxidative stress ,Endothelial dysfunction ,Serum Glucocorticoid Kinase-1 ,Settore MED/04 - Patologia Generale ,chemistry.chemical_classification ,Reactive oxygen species ,Kinase ,SGK ,General Medicine ,medicine.disease ,Serum Glucocorticoid Kinase-1, endothelial dysfunction, oxidative stress, type 2 diabetes, hyperglycaemia ,Cell biology ,Endothelial stem cell ,Glucose ,chemistry ,Hyperglycemia ,type 2 diabetes ,hyperglycaemia ,Oxidative stress ,Diabetic vascular disease - 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-1Delta60 (lacking of the N-60 amino acids-increase SGK-1 activity) or SGK-1Delta60KD (kinase-dead constructs). We tested our hypothesis in vitro after high glucose and glucosamine incubation. Increase in SGK-1 expression and activity (SGK-1Delta60) 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-1Delta60 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.
- Published
- 2014
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