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

Atsushi Masamune, Kenichi Satoh, Yoshitaka Sakai, Masayoshi Yoshida, Akihiko Satoh, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Introduction: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-activated transcription factor that controls growth, differentiation, and inflammation in different tissues. Roles of PPAR-γ activation in pancreatic acinar cells are poorly characterized. Aims: To examine the effects of PPAR-γ activation on the induction of apoptosis in rat pancreatic AR42J cells. Methodology: AR42J cells were treated with ligands of PPAR-γ, and induction of apoptosis was evaluated by cell viability, DNA-fragmentation, and flow cytometry. Results: Treatment of the cells with ligands of PPAR-γ (15-deoxy-Δ12, 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-fluormethylketone). 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-κB, suggesting a role of NF-κB-independent pathways. In AR42J cells and isolated pancreatic acini, PPAR-γ gene and protein were detected. In addition, troglitazone increased the PPAR-dependent transcriptional activity, suggesting that PPAR-γ is functional in AR42J cells. Conclusion: These results indicate that activation of PPAR-γ induces apoptosis in AR42J cells and imply that PPAR-γ may be a potential therapeutic target of pancreatic inflammation, because of its anti-inflammatory effects in addition to its proapoptotic effects.

Original languageEnglish
Pages (from-to)130-138
Number of pages9
Issue number2
Publication statusPublished - 2002


  • Apoptosis
  • AR42J cells
  • Pancreatitis
  • Peroxisome proliferator-activated receptorgamma
  • Troglitazone


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