EFFECTS OF CYCLOHEXIMIDE ON PANCREATIC ENDONUCLEASE ACTIVITY, APOPTOSIS, AND SEVERITY OF ACUTE-PANCREATITIS

The factors that determine the severity of acute pancreatitis are unkn own, but a close inverse correlation between that severity and the ext ent of acinar cell apoptosis that follows the triggering signal has be en previously noted [A. M. Kaiser, A. K. Saluja, A. Sengupta, M. Saluj a, and M. L. Steer. Am. J. Physiol. 269 (Cell Physiol. 38): C1295-C130 4, 1995]. In the present studies, we have evaluated internucleosomal D NA fragmentation and apoptosis within the pancreas and the effects of inhibiting protein synthesis by cycloheximide (CHX) on these phenomena as well as on the severity of pancreatitis. We report the constitutiv e presence of a Ca2+- and Mg2+-dependent endonuclease activity within pancreatic nuclei that is dependent on continued protein synthesis. Fu rthermore, we have found that CHX administration reduces the extent of apoptosis but significantly worsens the severity of pancreatitis that follows ligation of the rat common bile-pancreatic duct. These observ ations are consistent with the hypothesis that apoptosis is a teleolog ically beneficial response to acinar cell injury during acute pancreat itis.