Korean J Gastroenterol.  2001 Dec;38(6):427-432.

The Role of Nuclear Factor kB and Phosphatidylinositol 3 - kinase in Trypsinogen Activation in Cerulein - Stimulated Rat Pancreatic Acini

• Kim YJ
• Kim YT
• Hwang JH
• Kim J
• Jeong JB
• Yoon YB
• Kim CY

Abstract

BACKGROUND/AIMS: Intra-acinar cell activation of trypsinogen is a critical event in cerulein-induced pancreatitis. However, little is known about the intracellular signal transduction systems involved in trypsinogen activation. This study focused on the role of NF-kB and PI3-K involved in intracellular signal transduction systems to activate trypsinogen.
METHODS
Pancreatic acinar cells were prepared from male Wistar rats and nuclear factor kB (NF-kB) inhibitor, pyrolidine dithiocarbamate and N-acetylcysteine, or phosphatidylinositol 3-kinase (PI3-K) inhibitor, wortmannin and LY294002 were applied to each of a series of acinar cell cultures. Then, a supraphysiological (100 nM) concentration of cerulein was applied to the pretreated cells and the untreated control cells. Trypsinogen activation was detected by measuring trypsin activity from acinar cell homogenates and expressed as % of cerulein stimulated cells. The level of NF-kB activity was checked for the nuclear extracts, using electrophoretic mobility shift assay.
RESULTS
NF-kB activation in the acinar cells after cerulein hyperstimulation displayed a biphasic process over time. Both NF-kB inhibitors partially suppressed trypsinogen activation while the PI3-K inhibitors inhibited trypsinogen activation almost completely. NF-kB activity was blocked by pyrolidine dithiocarbamate or N-acetylcysteine but not by wortmannin or LY294002.
CONCLUSIONS
Trypsinogen is activated in cerulein hyperstimulated acinar cells by PI3-K or NF-kB pathway, independently.

MeSH Terms

Acetylcysteine
Acinar Cells
Animals
Ceruletide*
Electrophoretic Mobility Shift Assay
Humans
Male
NF-kappa B
Pancreatitis
Phosphatidylinositol 3-Kinase
Phosphatidylinositols*
Phosphotransferases*
Rats*
Rats, Wistar
Signal Transduction
Trypsin
Trypsinogen*
Acetylcysteine
Ceruletide
NF-kappa B
Phosphatidylinositol 3-Kinase
Phosphatidylinositols
Phosphotransferases
Trypsin
Trypsinogen