Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia

Francesca Ferrelli, Donatella Pastore, Barbara Capuani, Marco F. Lombardo, Marcel Blot-Chabaud, Andrea Coppola, Katia Basello, Angelica Galli, Giulia Donadel, Maria Romano, Sara Caratelli, Francesca Pacifici, Roberto Arriga, Nicola Di Daniele, Paolo Sbraccia, Giuseppe Sconocchia, Alfonso Bellia, Manfredi Tesauro, Massimo Federici, David Della MorteDavide Lauro

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)55-64
Number of pages10
JournalActa Diabetologica
Volume52
Issue number1
DOIs
StatePublished - 2015
Externally publishedYes

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Hyperglycemia
Glucocorticoids
Oxidative Stress
Endothelial Cells
Apoptosis
Nitric Oxide
Glucosamine
Reactive Oxygen Species
serum-inducible kinase
Phosphotransferases
Noxae
Umbilicus
Diabetic Angiopathies
Protein-Serine-Threonine Kinases
Nitric Oxide Synthase Type II
Retroviridae
Blood Vessels
Cell Survival
Insulin
Glucose

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 journalArticle

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 2015, 'Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia', Acta Diabetologica, vol. 52, no. 1, pp. 55-64. https://doi.org/10.1007/s00592-014-0600-4
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. / Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia. In: Acta Diabetologica. 2015 ; Vol. 52, No. 1. pp. 55-64.
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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

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