Pancreatic effects of ethionine: Blockade of exocytosis and appearance of crinophagy and autophagy precede cellular necrosis

H. Koike, M. L. Steer, J. Meldolesi

Research output: Contribution to journalArticle

Abstract

Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet for 24 h develop hemorrhagic pancreatic necrosis with a 5-day mortality rte of ~50%. At the end of the diet administration, the in vivo discharge of digestive enzymes is blocked, images of exocytosis and luminal membrane recycling disappear, and zymogen granules accumulate within acinar cells. The general ultrastructure, however, remains well preserved, protein synthesis is normal, and intracellular transport of secretory proteins is only slightly retarded. Thus, the CDE diet does not affect the general phenomenon of membrane fusion-fission but specifically inhibits that associated with exocytosis. Twenty-four hours after withdrawal of the CDE diet, discharge of zymogen granules into lysosomes (crinophagy) can be observed, and, 24 h later, autophagocytosis is noted. Finally, shortly before the onset of pancreatic necrosis, cells of nearly normal appearance are noted to be scattered among cells showing varying degrees of lesion up to complete disruption. Thus, the CDE-induced pancreatic necrosis results from a sequence of events: blockade of exocytosis evolves to crinophagy and autophagy, which might lead to lysosomal activation of zymogens.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume5
Issue number4
Publication statusPublished - 1982

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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