title: Effects of antioxidants on glucose-induced oxidative stress and endoplasmic reticulum stress in endothelial cells.
abstract: OBJECTIVE
  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 (5.5mM) or supra-physiological (27.5mM) 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 5.5mM 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.
authors: Department of Medicine, University of Florida, Jacksonville, United States. mae.sheikh-ali@jax.ufl.edu
authors: Mae
authors: M
authors: Sheikh-Ali
authors: Senan
authors: S
authors: Sultan
authors: Abdul-Razzak
authors: AR
authors: Alamir
authors: Michael J
authors: MJ
authors: Haas
authors: Arshag D
authors: AD
authors: Mooradian
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D051272:Glucose Transporter Type 1 / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007700:Kinetics; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010617:Phenanthridines / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014471:Umbilical Veins; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D051272:Glucose Transporter Type 1; D010617:Phenanthridines; D017382:Reactive Oxygen Species; C058428:hydroethidine; D000469:Alkaline Phosphatase; D024502:alpha-Tocopherol; D005947:Glucose; D001205:Ascorbic Acid