THE aim of this study was to define the effects of a potent inhibitor
of tyrosine phosphatases, sodium orthovanadate (0.1-100 mu M for up to
48 h), on dentate gyrus cells (DGC) in culture. Treatment with 100 mu
M orthovanadate evoked a delayed form of cell death. To examine the p
ossible 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 b
oth 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 orthovanada
te-induced death of DGC bears features of apoptosis.