title: Effect of thiazolidinedione on the proliferation of bovine retinal endothelial cells stimulated by vascular endothelial cell growth factor.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. gt-hiroishi@jcom.home.ne.jp
authors.forename: Goro
authors.initials: G
authors.lastname: Hiroishi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Murata
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: 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*
chemical_list: 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