title: Constant and intermittent high glucose enhances endothelial cell apoptosis through mitochondrial superoxide overproduction.
abstract: BACKGROUND
  It has been previously shown that hyperglycemia enhances free radical production, inducing oxidative damage, which in its turn activates the death pathways implicated in cell apoptosis and necrosis. But the possible involvement of this pathway in the hyperglycemia-induced apoptosis of endothelial cells has not yet been reported.
  
  
  METHODS
  To verify a possible connection between mitochondrial ROS production and apoptosis induced by both stable and oscillating high glucose, SOD, MnTBAP and TTFA was added to HUVEC cell culture medium. We measured nitrotyrosine and 8OHdG as oxidative stress parameters and Bcl-2 expression and Caspase-3 expression and activity as apoptosis indicators.
  
  
  RESULTS
  Our results show that hyperglycemia, both stable or oscillating, increases oxidative stress and endothelial cell apoptosis through ROS overproduction at the mitochondrial transport chain level.
  
  
  CONCLUSIONS
  The prevention of mitochondrial oxidative damage seems to be a future important therapeutic strategy in diabetes.
authors.affiliation: Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Piconi
authors.forename: Lisa
authors.initials: L
authors.lastname: Quagliaro
authors.forename: Roberta
authors.initials: R
authors.lastname: Assaloni
authors.forename: Roberto
authors.initials: R
authors.lastname: Da Ros
authors.forename: Amabile
authors.initials: A
authors.lastname: Maier
authors.forename: Gianni
authors.initials: G
authors.lastname: Zuodar
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014471:Umbilical Veins
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D013481:Superoxides; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005947:Glucose