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Ca 2+ ‐induced pancreatic cell death: Roles of the endoplasmic reticulum, zymogen granules, lysosomes and endosomes
Author(s) -
Petersen Ole H
Publication year - 2008
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2007.05281.x
Subject(s) - endoplasmic reticulum , trypsinogen , endosome , vacuole , microbiology and biotechnology , endocytic cycle , zymogen , intracellular , biochemistry , secretion , endocytosis , biology , enzyme , cytoplasm , cell , trypsin
Alcohol induces Ca 2+ ‐dependent intracellular trypsinogen activation in the apical granular area via non‐oxidative metabolites, such as fatty acid ethyl esters and fatty acids. Intracellular trypsinogen activation is a crucial initiating event in the development of acute pancreatitis, but the specific organelle in which this process takes place has been unknown. Recent data demonstrate that the Ca 2+ ‐dependent trypsinogen activation occurs in postexocytotic endocytic vacuoles. These vacuoles are acid due to a bafilomycin‐sensitive vacuolar H + ATPase and have a very Ca 2+ ‐permeable membrane. Acid endocytic structures, together with lysosomes, zymogen granules and elements of the endoplasmic reticulum, also play an important role in the physiological Ca 2+ signal generation that normally regulates enzyme and fluid secretion from the exocrine pancreas.