PUTATIVE MORPHOGEN, DIF, OF DICTYOSTELIUM-DISCOIDEUM INDUCES APOPTOSIS IN RAT PANCREATIC AR42J CELLS

We have recently shown that differentiation-inducing factor-1 (DIF-1) of Dictyostelium discoideum is capable of raising intracellular calciu m concentration ([Ca2+](i)) and suppressing cell proliferation of rat pancreatic AR42J cells in a dose-dependent manner, and that DIF-1 at a concentration of 40 mu mol/L is toxic to the cells. In this study, we have further characterized the cytotoxic effect of DIF-1 on AR42J cel ls and have analyzed the effect of DIF-1 on [Ca2+](i). In the presence of 40 mu mol/L DIF-1, cells began to bleb after approximately 6 h, an d most had died within 48 h. Biochemical analysis revealed that DNA fr agmentation was accompanied by cell death. Monitoring the changes in [ Ca2+](i) induced by DIF-1, it was found that cells were able to adapt to stimulation with DIF-1 so that they did not respond to subsequent s timulation by DIF-1. These results indicate that DIF-1 induced apoptos is in AR42J cells probably via a cell signaling system.