Effects of cycloheximide on pancreatic endonuclease activity, apoptosis, and severity of acute pancreatitis

Andreas M. Kaiser, Ashok K. Saluja, Li Lu, Kenji Yamanaka, Yoshikazu Yamaguchi, Michael L. Steer

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The factors that determine the severity of acute pancreatitis are unknown, but a close inverse correlation between that severity and the extent of acinar cell apoptosis that follows the triggering signal has been previously noted [A. M. Kaiser, A. K. Saluja, A. Sengupta, M. Saluja, and M. L. Steer. Am. J. Physiol. 269 (Cell Physiol. 38): C1295-C1304, 1995]. In the present studies, we have evaluated internucleosomal DNA 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 constitutive presence of a Ca2+- and Mg2+- dependent endonuclease activity within pancreatic nuclei that is dependent on continued protein synthesis. Furthermore, 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 observations are consistent with the hypothesis that apoptosis is a teleologically beneficial response to acinar cell injury during acute pancreatitis.

Original languageEnglish (US)
Pages (from-to)C982-C993
JournalAmerican Journal of Physiology - Cell Physiology
Volume271
Issue number3 40-3
DOIs
StatePublished - Sep 1996

Keywords

  • acinar cell
  • acute disease
  • bile- pancreatic duct obstruction necrosis
  • cell death
  • inhibition of protein synthesis
  • pancreas

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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