AJP - Cell Physiology, Vol 271, Issue 3 C982-C993, Copyright © 1996 by American Physiological Society

ARTICLES

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

A. M. Kaiser, A. K. Saluja, L. Lu, K. Yamanaka, Y. Yamaguchi and M. L. Steer
Department of Surgery, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, USA.

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 Ca(2+)- and Mg(2+)-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.

This article has been cited by other articles:

				G. Gomez, H.-M. Lee, Q. He, E. W. Englander, T. Uchida, and G. H. Greeley Jr. Acute Pancreatitis Signals Activation of Apoptosis-Associated and Survival Genes inMice Experimental Biology and Medicine, July 1, 2001; 226(7): 692 - 700. [Abstract] [Full Text] [PDF]