Document Detail

Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL).
MedLine Citation:
PMID:  19779015     Owner:  NLM     Status:  MEDLINE    
Mechanisms leading to acute pancreatitis after a fat-enriched meal combined with excess alcohol are incompletely understood. We have studied the effects of alcohol and fat (VLDL) on pancreatic acinar cell (PAC) function, oxidative stress, and repair mechanisms by pancreatic stellate cells (PSC) leading to fibrogenesis. To do so, PAC (rat) were isolated and cultured up to 24 h. Ethanol and/or VLDL were added to PAC. We measured PAC function (amylase, lipase), injury (lactic dehydrogenase), apoptosis (TUNEL, Apo2.7, annexin V binding), oxidative stress, and lipid peroxidation (conjugated dienes, malondialdehyde, chemoluminescence); we also measured PSC proliferation (bromodeoxyuridine incorporation), matrix synthesis (immunofluorescence of collagens and fibronectin, fibronectin immunoassay), and fatty acids in PAC supernatants (gas chromatography). Within 6 h, cultured PAC degraded and hydrolyzed VLDL completely. VLDL alone (50 microg/ml) and in combination with alcohol (0.2, 0.5, and 1% vol/vol) induced PAC injury (LDL, amylase, and lipase release) within 2 h through generation of oxidative stress. Depending on the dose of VLDL and alcohol, apoptosis and/or necrosis were induced. Antioxidants (Trolox, Probucol) reduced the cytotoxic effect of alcohol and VLDL. Supernatants of alcohol/VLDL-treated PAC stimulated stellate cell proliferation and extracellular matrix synthesis. We concluded that, in the presence of lipoproteins, alcohol induces acinar cell injury. Our results provide a biochemical pathway for the clinical observation that a fat-enriched meal combined with excess alcohol consumption can induce acinar cell injury (acute pancreatitis) followed by repair mechanisms (proliferation and increased matrix synthesis in PSC).
Marco Siech; Zhengfei Zhou; Shaoxia Zhou; Bernd Bair; Andreas Alt; Stefan Hamm; Hans Gross; Jens Mayer; Hans G Beger; Xiaodong Tian; Marko Kornmann; Max G Bachem
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Publication Detail:
Type:  Journal Article     Date:  2009-09-24
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  297     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-01     Completed Date:  2009-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G1163-71     Citation Subset:  IM    
Dept. of General and Vascular Surgery, Ostalb-Klinikum Aalen, Germany.
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MeSH Terms
Acute Disease
Amylases / metabolism
Apoptosis / drug effects
Cell Proliferation / drug effects*
Cells, Cultured
Dose-Response Relationship, Drug
Ethanol / toxicity*
Extracellular Matrix / metabolism*
L-Lactate Dehydrogenase / metabolism
Lipase / metabolism
Lipid Peroxidation / drug effects
Lipoproteins, VLDL / metabolism,  toxicity*
Oxidative Stress / drug effects
Pancreas, Exocrine / drug effects*,  metabolism,  pathology
Pancreatitis / etiology*,  metabolism,  pathology
Rats, Wistar
Time Factors
Reg. No./Substance:
0/Lipoproteins, VLDL; 64-17-5/Ethanol; EC Dehydrogenase; EC; EC 3.2.1.-/Amylases

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