Ligands of peroxisome proliferator-activated receptor-gamma induce apoptosis in AR42J cells.

Abstract

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor that controls growth, differentiation, and inflammation in different tissues. Roles of PPAR-gamma activation in pancreatic acinar cells are poorly characterized. To examine the effects of PPAR-gamma activation on the induction of apoptosis in rat pancreatic AR42J cells. AR42J cells were treated with ligands of PPAR-gamma, and induction of apoptosis was evaluated by cell viability, DNA-fragmentation, and flow cytometry. Treatment of the cells with ligands of PPAR-gamma (15-deoxy-open triangle12,14-prostaglandin J2 or troglitazone) induced apoptosis in a dose-dependent manner. Troglitazone-induced apoptosis was not blocked by inhibitors of caspases (acetyl-DEVD-aldehyde and benzoyloxycarbonyl-VAD-fluoromethylketone). Troglitazone induced the expression of pancreatitis-associated protein-1 and clusterin mRNAs. Troglitazone activated c-Jun NH2-terminal kinase/stress-activated protein kinase, but inhibited the activation of extracellular signal-regulated kinases 1/2. Troglitazone did not activate NF-kappaB, suggesting a role of NF-kappaB-independent pathways. In AR42J cells and isolated pancreatic acini, PPAR-gamma gene and protein were detected. In addition, troglitazone increased the PPAR-dependent transcriptional activity, suggesting that PPAR-gamma is functional in AR42J cells. These results indicate that activation of PPAR-gamma induces apoptosis in AR42J cells and imply that PPAR-gamma may be a potential therapeutic target of pancreatic inflammation, because of its anti-inflammatory effects in addition to its proapoptotic effects.