Oxidative stress in response to high glucose levels in endothelial cells and in endothelial progenitor cells: evidence for differential glutathione peroxidase-1 expression.
Endothelial cells and endothelial progenitor cells (EPCs) play a key role in the pathogenesis of vascular disease. Both cell types are affected by the oxidative stress but their susceptibility may be different. This study aimed to investigate the antioxidative enzymes activated in EPCs after high constant glucose exposure as compared to endothelial cells (HUVECs). Both cells were incubated in the presence of normal (5mM) and high constant (25mM) d-glucose, as well as l-glucose as osmotic control for 48 and 96h. After a 48-hour exposure to high d-glucose, cell viability was significantly decreased both in EPCs and HUVECs as compared with normal d-glucose (p<0.01). However, after 96h there was no difference between EPCs grown on normal or high d-glucose, while HUVEC viability was affected by high d-glucose at 96h too (p<0.001). High d-glucose exposure induced a significant increase in reactive oxygen species (ROS) production in both cell types at 48h; however, after 96h, a significant decrease in ROS production (p<0.01) and a parallel marked increase in glutathione peroxidase type 1 (GPx-1) expression (p<0.01) and activity (p<0.01) were observed in EPCs compared to HUVECs. These data suggest that EPCs have a well-adaptive response to oxidative stress induced by constant and sustained high glucose exposure. This resistance to high glucose levels might be due to increased expression and activity of glutathione peroxidase allowing better cell survival.
Felice
Francesca
F
Cardiac, Thoracic and Vascular Department, Cardiovascular Research Laboratory, University of Pisa, Pisa, Italy.
Lucchesi
Daniela
D
di Stefano
Rossella
R
Barsotti
Maria Chiara
MC
Storti
Eugenia
E
Penno
Giuseppe
G
Balbarini
Alberto
A
Del Prato
Stefano
S
Pucci
Laura
L
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
D015415:Biomarkers; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D005947:Glucose; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human