| Supraphysiologic concentrations of cerulein induce apoptosis in the rat pancreatic acinar cell line AR4-2J. | |
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MedLine Citation:
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PMID: 10416696 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Little is known as yet about the role of apoptosis in pancreatic damage. This study evaluated the effects of supraphysiologic concentrations of the cholecystokinin (CCK) analog, cerulein, which causes cell damage in vitro and acute pancreatitis in vivo, on cell proliferation and DNA fragmentation in the rat pancreatic acinar cell line AR4-2J. Cerulein inhibited the cell proliferation of AR4-2J time- and dose-dependently to approximately 60% of the control level at 10(-6) M after 72 h. DNA fragmentation, as assessed by both electrophoresis and enzyme-linked immunosorbent assay (ELISA), occurred at cerulein concentrations > or = 10(-8) M. The maximal DNA fragmentation as measured by ELISA was reached after 24 h. Cerulein at concentrations > or = 10(-9) M induced wild-type p53. Glutathione (1 mM) diminished the effects of cerulein on both cell proliferation and DNA fragmentation, whereas spermine (100 microM), which partially attenuated DNA fragmentation, did not have an effect on cell proliferation. The CCK-A-receptor antagonist loxiglumide completely abolished the effect of cerulein on DNA fragmentation. The serine-protease inhibitor FUT-175 (10 microM), the cysteine-protease inhibitor NCO-700 (5 mM), and ethylene glycol tetraacetic acid (EGTA; 500 microM) all had no effects on the changes in cell proliferation and DNA fragmentation induced by cerulein. The data suggest that supraphysiologic concentrations of cerulein rapidly induce apoptosis in AR4-2J cells and only later inhibit cell proliferation. These effects are mediated by CCK-A receptors. Cerulein-induced apoptosis may involve the induction of wild-type p53 or glutathione depletion or both. |
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Authors:
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N Sata; H Klonowski-Stumpe; B Han; R Lüthen; D Häussinger; C Niederau |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pancreas Volume: 19 ISSN: 0885-3177 ISO Abbreviation: Pancreas Publication Date: 1999 Jul |
Date Detail:
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Created Date: 1999-08-26 Completed Date: 1999-08-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8608542 Medline TA: Pancreas Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 76-82 Citation Subset: IM |
Affiliation:
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Department of Medicine, Heinrich-Heine-University of Düsseldorf, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Blotting, Western Caerulein / pharmacology* Cell Division / drug effects Cell Survival / drug effects DNA / analysis Dose-Response Relationship, Drug Egtazic Acid / pharmacology Electrophoresis, Polyacrylamide Gel Enzyme-Linked Immunosorbent Assay Gastrointestinal Agents / pharmacology* Glutathione / pharmacology Pancreas / cytology, drug effects* Protease Inhibitors / pharmacology Rats Spermine / pharmacology Time Factors Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Gastrointestinal Agents; 0/Protease Inhibitors; 17650-98-5/Caerulein; 67-42-5/Egtazic Acid; 70-18-8/Glutathione; 71-44-3/Spermine; 9007-49-2/DNA |
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