Effect of Thiazolidinedione on the Proliferation of Bovine Retinal Endothelial Cells Stimulated by Vascular Endothelial Cell Growth Factor

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To investigate the effect of troglitazone, an antidiabetic drug, on the cytosolic Ca(2+) concentrations ([Ca(2+)]i) and the cell cycles of bovine retinal endothelial cells (RECs) stimulated with vascular endothelial growth factor (VEGF). The changes in [Ca(2+)]i were monitored using microfluorometry with Fura-2. The phase of the cell cycle was examined by an immunocytochemical analysis using monoclonal antibodies against cell cycle-specific nuclear antigens. In the presence of extracellular Ca(2+), VEGF-induced transient [Ca(2+)]i elevation followed by continuous steady-state elevation resulted in cell cycle progression in RECs. The removal of extracellular Ca(2+) inhibited the continuous component, but transient [Ca(2+)]i elevation was still observed. These results are compatible with the hypothesis that a continuous steady-state elevation of [Ca(2+)]i may be mediated mainly through the influx of extracellular Ca(2+). Pretreatment with 10 microM troglitazone prevented the transient and continuous steady-state elevation of [Ca(2+)]i, resulting in an inhibition of the cell cycle in RECs stimulated with VEGF. These data suggest that troglitazone inhibits VEGF-induced cell cycle progression through the inhibition of [Ca(2+)]i in RECs.