Effect of thiazolidinedione on the proliferation of bovine retinal endothelial cells stimulated by vascular endothelial cell growth factor.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
These data suggest that troglitazone inhibits VEGF-induced cell cycle progression through the inhibition of [Ca(2+)]i in RECs.
Hiroishi
Goro
G
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. gt-hiroishi@jcom.home.ne.jp
Murata
Toshinori
T
Ishibashi
Tatsuro
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008024:Ligands; D011994:Recombinant Proteins / Q000494:pharmacology; D012171:Retinal Vessels / Q000166:cytology*; D013050:Spectrometry, Fluorescence; D045162:Thiazolidinediones / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D008024:Ligands; D011994:Recombinant Proteins; D045162:Thiazolidinediones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C089946:2,4-thiazolidinedione; D002118:Calcium; D016257:Fura-2