Document Detail

Activation of mitogen-activated protein kinases in different models of pancreatic acinar cell damage.
MedLine Citation:
PMID:  10923358     Owner:  NLM     Status:  MEDLINE    
Mitogen-activated protein kinase (MAPK) family members, namely MAPK, c-Jun NH2-terminal protein kinase (JNK), and p38MAPK, have been recently reported to have opposing effects on apoptosis. AIM: To determine the activity of MAPKs and the level of Bax, Bcl-2 and p53--proteins known to be involved in the regulation of apoptosis--in pancreatic acini subjected to stressful stimuli leading to cell death. METHODS AND RESULTS: Isolated pancreatic acini were irradiated for 30 min with ultraviolet B (UV-B) or stimulated with supraphysiological concentrations of cholecystokinin (CCK). As it was assessed by means of acridine orange/ethidium bromide staining, irradiation with UV-B induced predominantly apoptosis while necrosis predominated in CCK-stimulated acini. The activity of MAPK, JNK and p38MAPK was determined by means of Western-blotting, with the use of antibodies which recognize active, dually phosphorylated enzymes. Irradiation with UV-B induced a rapid, 3-fold increase in MAPK activity. It had a maximum at 30 min and then gradually declined to reach the normal level at 120 min. Concomitantly, early activation of p38-MAPK was found at 30 min. However, unlike MAPK, p38-MAPK activity was then gradually rising to reach a maximum (5-fold increase) at 180 min. UV-B-induced activation of both kinases was not affected by the pretreatment with antioxidant--N-acetylo-L-cysteine or protein kinase C inhibitor--GF-109203X. In UV-B-irradiated cells, we did not detect any significant JNK activation as well as any significant changes in Bax, Bcl-2 and p53 levels assessed by means of Western-blotting. CONCLUSION: It seems likely that a specific interaction between MAPK and p38MAPK signaling pathway may be involved in the determination of the cell death mechanism in pancreatic acini subjected to stressful stimuli.
A Dabrowski; I Tribillo; M I Dabrowska; U Wereszczynska-Siemiatkowska; A Gabryelewicz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Zeitschrift für Gastroenterologie     Volume:  38     ISSN:  0044-2771     ISO Abbreviation:  Z Gastroenterol     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-10-19     Completed Date:  2000-10-19     Revised Date:  2009-11-11    
Medline Journal Info:
Nlm Unique ID:  0033370     Medline TA:  Z Gastroenterol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  469-81     Citation Subset:  IM    
Department of Gastroenterology, Medical School of Bialystok, Poland.
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MeSH Terms
Apoptosis / drug effects,  physiology*,  radiation effects
Cell Death / drug effects,  physiology,  radiation effects
Cholecystokinin / pharmacology
Enzyme Activation / drug effects,  radiation effects
MAP Kinase Signaling System / drug effects,  physiology*,  radiation effects
Pancreas / cytology*,  drug effects,  radiation effects
Proto-Oncogene Proteins / physiology
Proto-Oncogene Proteins c-bcl-2 / physiology
Rats, Wistar
Tumor Suppressor Protein p53 / physiology
Ultraviolet Rays
bcl-2-Associated X Protein
Reg. No./Substance:
0/Bax protein, rat; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 9011-97-6/Cholecystokinin

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