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<sup>+</sup>–K<sup>+</sup> 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<sup>+</sup>−K<sup>+</sup> 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 55-64 |
| Number of pages | 10 |
| Journal | Acta Diabetologica |
| Volume | 52 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2015 |
| Externally published | Yes |
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Keywords
- Endothelial dysfunction
- Hyperglycaemia
- Oxidative stress
- Serum glucocorticoid kinase-1
- Type 2 diabetes
ASJC Scopus subject areas
- Endocrinology
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia. / Ferrelli, Francesca; Pastore, Donatella; Capuani, Barbara; Lombardo, Marco F.; Blot-Chabaud, Marcel; Coppola, Andrea; Basello, Katia; Galli, Angelica; Donadel, Giulia; Romano, Maria; Caratelli, Sara; Pacifici, Francesca; Arriga, Roberto; Di Daniele, Nicola; Sbraccia, Paolo; Sconocchia, Giuseppe; Bellia, Alfonso; Tesauro, Manfredi; Federici, Massimo; Della Morte, David; Lauro, Davide.
In: Acta Diabetologica, Vol. 52, No. 1, 2015, p. 55-64.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia
AU - Ferrelli, Francesca
AU - Pastore, Donatella
AU - Capuani, Barbara
AU - Lombardo, Marco F.
AU - Blot-Chabaud, Marcel
AU - Coppola, Andrea
AU - Basello, Katia
AU - Galli, Angelica
AU - Donadel, Giulia
AU - Romano, Maria
AU - Caratelli, Sara
AU - Pacifici, Francesca
AU - Arriga, Roberto
AU - Di Daniele, Nicola
AU - Sbraccia, Paolo
AU - Sconocchia, Giuseppe
AU - Bellia, Alfonso
AU - Tesauro, Manfredi
AU - Federici, Massimo
AU - Della Morte, David
AU - Lauro, Davide
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Endothelial dysfunction
KW - Hyperglycaemia
KW - Oxidative stress
KW - Serum glucocorticoid kinase-1
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84939874704&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939874704&partnerID=8YFLogxK
U2 - 10.1007/s00592-014-0600-4
DO - 10.1007/s00592-014-0600-4
M3 - Article
C2 - 24961472
AN - SCOPUS:84939874704
VL - 52
SP - 55
EP - 64
JO - Acta Diabetologica
JF - Acta Diabetologica
SN - 0940-5429
IS - 1
ER -