Effects of antioxidants on glucose-induced oxidative stress and endoplasmic reticulum stress in endothelial cells

Aim: Hyperglycemia-induced endothelial cell dysfunction can be the result of increased oxidative stress and concomitant increase in endoplasmic reticulum (ER) stress. To test the extent of coupling between these two stresses, the effect of antioxidant vitamins on glucose-induced oxidative stress and ER stress in endothelial cells were studied. Methods: Human umbilical vein endothelial cells (HUVEC) were treated with physiological (5.5 mM) or supra-physiological (27.5 mM) dextrose concentrations, and ER stress and oxidative stress were measured. Additional experiments were carried out in HUVEC over-expressing exogenous glucose transporter-1 (Glut-1) and treated with 5.5 mM dextrose. Results: Supra-physiological dextrose concentrations increased both ER stress and oxidative stress. However, while oxidative stress could be effectively inhibited with alpha-tocopherol and ascorbic acid, these antioxidants had no effect on ER stress. Increasing intracellular glucose levels by exogenous expression of Glut-1 in endothelial cells also increased oxidative stress and ER stress. Whereas the oxidative stress in these cells was reduced with alpha-tocopherol and ascorbic acid and dimethylsulfoxide, the ER stress could not be ameliorated with alpha-tocopherol and ascorbic acid. Conclusions: These results indicate that ER stress can be uncoupled from oxidative stress and antioxidants can ameliorate the latter without altering the ER stress induced by hyperglycemia. Published by Elsevier Ireland Ltd.