Document Detail

Cholecystokinin-8-induced hypoplasia of the rat pancreas: influence of nitric oxide on cell proliferation and programmed cell death.
MedLine Citation:
PMID:  15504154     Owner:  NLM     Status:  MEDLINE    
The background of cholecystokinin-8 (CCK-8)-induced hypoplasia in the pancreas is not known. In order to increase our understanding we studied the roles of nitric oxide and NF-kappaB in rats. CCK-8 was injected for 4 days, in a mode known to cause hypoplasia, and the nitric oxide formation was either decreased by means of N(omega)-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). The activation of NF-kappaB was quantified by ELISA detection, apoptosis with caspase-3 and histone-associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells were visualized by the incorporation of [(3)H]-thymidine. Pancreatic histology and weight as well as protein- and DNA contents were also studied. Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and nuclear factor kappaB (NF-kappaB) activation. It also caused vacuolisation of acinar cells. The inhibition of endogenous nitric oxide formation by L-NNA further increased apoptosis and NF-kappaB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased apoptosis and other pathways of cell death, raised proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Histological examination showed no inflammation in any group. We conclude that during CCK-8-induced pancreatic hypoplasia, endogenously formed nitric oxide suppresses apoptosis but increases cell death along non-apoptotic pathways and stimulates regeneration of acinar cells. Exogenous nitric oxide enhances the acinar cell turnover by increasing both apoptotic and non-apoptotic cell death and cell renewal. In this situation NF-kappaB activation seems not to inhibit apoptosis nor promote cell proliferation.
Lena M Trulsson; Thomas Gasslander; Joar Svanvik
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  95     ISSN:  1742-7835     ISO Abbreviation:  Basic Clin. Pharmacol. Toxicol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-26     Completed Date:  2005-03-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  183-90     Citation Subset:  IM    
Department of Biomedicine and Surgery, Faculty of Health Sciences, University Hospital, SE-581 85 Linköping, Sweden.
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MeSH Terms
Apoptosis / drug effects*
Caspase 3
Caspases / metabolism
Cell Proliferation / drug effects*
DNA Fragmentation / drug effects
Histones / metabolism
Injections, Subcutaneous
NF-kappa B / metabolism
Nitric Oxide / metabolism*
Nitric Oxide Synthase / antagonists & inhibitors
Pancreas / cytology*,  drug effects*
Rats, Wistar
Sincalide / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Histones; 0/NF-kappa B; 10102-43-9/Nitric Oxide; 25126-32-3/Sincalide; EC Oxide Synthase; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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