Relationship between NF-kappaB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation.
Biochem Biophys Res Commun
; 280(1): 388-95, 2001 Jan 12.
Article
in En
| MEDLINE
| ID: mdl-11162528
Intra-acinar cell nuclear factor-kappaB (NF-kappaB) and trypsinogen activation are early events in secretagogue-induced acute pancreatitis. We have studied the relationship between NF-kappaB and trypsinogen activation in rat pancreas. CCK analogue caerulein induces early (within 15 min) parallel activation of both NF-kappaB and trypsinogen in pancreas in vivo as well as in pancreatic acini in vitro. However, NF-kappaB activation can be induced without trypsinogen activation by lipopolysaccharide in pancreas in vivo and by phorbol ester in pancreatic acini in vitro. Stimulation of acini with caerulein after 6 h of culture results in NF-kappaB but not trypsinogen activation. Protease inhibitors (AEBSF, TLCK, and E64d) inhibit both intracellular trypsin activity and NF-kappaB activation in caerulein stimulated acini. A chymotrypsin inhibitor (TPCK) inhibits NF-kappaB activation but not trypsin activity. The proteasome inhibitor MG-132 prevents caerulein-induced NF-kappaB activation but does not prevent trypsinogen activation. These findings indicate that although caerulein-induced NF-kappaB and trypsinogen activation are temporally closely related, they are independent events in pancreatic acinar cells. NF-kappaB activation per se is not required for the development of early acinar cell injury by supramaximal secretagogue stimulation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreas
/
Trypsinogen
/
Ceruletide
/
NF-kappa B
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2001
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos