Orthovanadate induces cell death in rat dentate gyrus primary culture.
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.
Figiel
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Nencki Institute, Warsaw, Poland.
Kaczmarek
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D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation; D018891:Dentate Gyrus / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology; D009336:Necrosis; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D019810:Sodium Azide / Q000633:toxicity; D014638:Vanadates / Q000633:toxicity*
D014638:Vanadates; D019810:Sodium Azide; D003513:Cycloheximide