Orthovanadate induces cell death in rat dentate gyrus primary culture

Neuroreport. 1997 Jul 28;8(11):2465-70. doi: 10.1097/00001756-199707280-00011.


The aim of this study was to define the effects of a potent inhibitor of tyrosine phosphatases, sodium orthovanadate (0.1-100 microM for up to 48 h), on dentate gyrus cells (DGC) in culture. Treatment with 100 microM orthovanadate evoked a delayed form of cell death. To examine the possible involvement of apoptosis in orthovanadate-induced cell death, biochemical and morphological alterations were compared with those of necrotic death induced by sodium azide. Phase-contrast microscopy and nuclear condensation analysis showed that orthovanadate and azide each evoked cell death by distinct pathways. TUNEL assay was positive in both cases. Application of a protein synthesis inhibitor, cycloheximide, did not prevent cytotoxicity caused by either orthovanadate or azide and potentiated the effects of vanadate. We conclude that orthovanadate-induced death of DGC bears features of apoptosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Cell Death / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cycloheximide / pharmacology
  • DNA Fragmentation
  • Dentate Gyrus / cytology*
  • Dose-Response Relationship, Drug
  • Hippocampus / cytology
  • Necrosis
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / pathology
  • Rats
  • Sodium Azide / toxicity
  • Vanadates / toxicity*


  • Vanadates
  • Sodium Azide
  • Cycloheximide