Metabolism-induced oxidative stress is a mediator of glucose toxicity in HT22 neuronal cells

Free Radic Res. 2009 Sep;43(9):876-86. doi: 10.1080/10715760903104374. Epub 2009 Jul 24.


Oxidative stress has been widely considered as a key player in the adverse effects of hyperglycaemia to various tissues, including neuronal cells. This study examined the participation of oxidative stress in injurious effects of high glucose on HT22 cells along with the activity of proteasome, a proteolytic system responsible for degradation of oxidized proteins. Although 10-fold glucose concentration caused non-significant viability changes, a significant reduction of cell proliferation was found. Moreover, the cell morphology was also altered. These changes were followed by an enhancement of intracellular ROS generation, however without any significant boost of the carbonyl group concentration in proteins. Correspondingly, only a slight decline in the 20S proteasome activity was found in high-glucose-treated cells. On the other hand, substances affecting glucose metabolism or antioxidants partially preserved the oxidative stress in high glucose treated cells. In summary, these results highlight the role of metabolic oxidative stress in hyperglycaemia affecting neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cell Line
  • Cell Proliferation
  • Cell Shape
  • Cell Survival
  • Enzyme Inhibitors / pharmacology
  • Glucose / metabolism*
  • Glycation End Products, Advanced / metabolism
  • Glycolysis* / drug effects
  • Hyperglycemia / metabolism*
  • Hyperglycemia / pathology
  • Mice
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxidative Stress* / drug effects
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Carbonylation
  • Reactive Oxygen Species / metabolism*
  • Time Factors


  • Antioxidants
  • Enzyme Inhibitors
  • Glycation End Products, Advanced
  • Reactive Oxygen Species
  • Proteasome Endopeptidase Complex
  • Glucose