Differential Effects of PPARγ Ligands on Oxidative Stress–Induced Death of Retinal Pigmented Epithelial Cells

摘要: PURPOSE To investigate the role of peroxisome proliferator-activated receptor (PPAR)-γ in modulating retinal pigmented epithelium (RPE) responses to oxidative stress. METHODS ARPE-19 cells were treated with oxidant, t-butylhydroperoxide (tBH) induce apoptosis. Cells pretreated synthetic PPARγ agonists antidiabetic thiazolidinediones class before tBH challenge assessed for viability and, by microarray analysis, effects on gene expression. RESULTS Treatment resulted a loss and global changes pattern ligands found have differential modulatory tBH-induced apoptosis RPE cells. Whereas rosiglitazone pioglitazone potentiated cell death, troglitazone acted as potent cytoprotective agent. Downregulation expression an siRNA enhanced death response treatment blocked effect consistent mediating this response. Microarray analysis revealed that while had little induced treatment, dramatically reduced number caused A unique subset genes deregulated selectively normalized identified. CONCLUSIONS These findings demonstrate can survival Oxidative stress leads deregulation large set specific these be modulated represent potential novel targets therapies.