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


OBJECTIVE
To examine the effects of PPAR-gamma activation on the induction of apoptosis in rat pancreatic AR42J cells.


METHODS
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.


CONCLUSIONS
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.
Masamune
Atsushi
A
Department 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
Satoh
Kenichi
K
Sakai
Yoshitaka
Y
Yoshida
Masayoshi
M
Satoh
Akihiko
A
Shimosegawa
Tooru
T
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D051152:Clusterin; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics; D020672:I-kappa B Proteins; D007155:Immunologic Factors / Q000494:pharmacology*; D008024:Ligands; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D009842:Oligopeptides / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology*; D000073718:Pancreatitis-Associated Proteins; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D000077288:Troglitazone
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000590:Amino Acid Chloromethyl Ketones; D017304:Annexin A5; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D002839:Chromans; D051152:Clusterin; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D020672:I-kappa B Proteins; D007155:Immunologic Factors; D008024:Ligands; D018832:Molecular Chaperones; C000606206:Nfkbia protein, rat; D009842:Oligopeptides; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C108637:aspartyl-glutamyl-valyl-aspartal; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000072000:NF-KappaB Inhibitor alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D000077288:Troglitazone; D015230:Prostaglandin D2