Constant and intermittent high glucose enhances endothelial cell apoptosis through mitochondrial superoxide overproduction

Diabetes Metab Res Rev. May-Jun 2006;22(3):198-203. doi: 10.1002/dmrr.613.

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.

Conclusion: The prevention of mitochondrial oxidative damage seems to be a future important therapeutic strategy in diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Cell Culture Techniques
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Glucose / pharmacology*
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Superoxides / metabolism*
  • Umbilical Veins

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Superoxides
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Glucose