Calcium-dependent apoptotic gene expression in cerulein-treated AR42J cells.

Elevated Ca(2+) concentrations within the pancreatic acinar cells represent a risk factor for the development of acute pancreatitis. Apoptosis is an important characteristic of pancreatitis, with induction of apoptotic genes and intraceullar increase of calcium, endonucleases, and protease. The present study, which aims to investigate whether (1) cerulein induces apoptotic gene expression (bax, bid, p53) in pancreatic acinar AR42J cells and (2) cerulein-induced gene expression is mediated by intracellular Ca(2+), monitored the gene expression profile in the cells treated with the Ca(2+) chelator BAPTA-AM. Results showed that cerulein (10(-7) M) evoked an initial peak Ca(2+) signal; a further Ca(2+) signal was induced with second treatment of cerulein. Cerulein-induced Ca(2+) signal could not be detected in the cells treated with the Ca(2+) chelator BAPTA-AM. Cerulein dose-dependently induced apoptosis, determined by DNA fragmentation and pro-apoptotic bid expression in AR42J cells. Cerulein induced bid, bax, and p53 mRNA expression, which was inhibited in the cells treated with cerulein and cultured in the presence of BAPTA-AM. The present results suggest that increase in the free cytosolic Ca(2+) may be the upstream event of apoptotic gene (bax, bid, p53) expression, which contribute to cerulein-induced apoptosis in pancreatic acinar cells.