Ligands of peroxisome proliferator-activated receptor-gamma induce apoptosis in AR42J cells
Related Experiment Videos
Atsushi Masamune1, Kenichi Satoh, Yoshitaka Sakai
1Department of Gastroenterology, Division of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Japan. amasamune@int3.med.tohoku.ac.jp
Introduction:
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.
Aims:
To examine the effects of PPAR-gamma activation on the induction of apoptosis in rat pancreatic AR42J cells.
Methodology:
AR42J cells were treated with ligands of PPAR-gamma, and induction of apoptosis was evaluated by cell viability, DNA-fragmentation, and flow cytometry.
Results:
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.
Conclusion:
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.
Related Concept Videos
Peroxisomes
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
Apoptosis
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized by phagocytes.
GPCR Desensitization