Relationship between NF-κB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation

Antti J. Hietaranta, Ashok Saluja, Lakshmi Bhagat, Vijay P. Singh, Albert M. Song, Michael L. Steer

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Intra-acinar cell nuclear factor-κB (NF-κB) and trypsinogen activation are early events in secretagogue-induced acute pancreatitis. We have studied the relationship between NF-κB and trypsinogen activation in rat pancreas. CCK analogue caerulein induces early (within 15 rain) parallel activation of both NF-κB and trypsinogen in pancreas in viva as well as in pancreatic acini in vitro. However, NF-κB activation can be induced without trypsinogen activation by lipopolysaccharide in pancreas in viva and by phorbol ester in pancreatic acini in vitro. Stimulation of acini with caerulein after 6 h of culture results in NF-κB but not trypsinogen activation. Protease inhibitors (AEBSF, TLCK, and E64d) inhibit both intracellular trypsin activity and NF-κB activation in caerulein stimulated acini. A chymotrypsin inhibitor (TPCK) inhibits NF-κB activation but not trypsin activity. The proteasome inhibitor MG-132 prevents caerulein-induced NF-κB activation but does not prevent trypsinogen activation. These findings indicate that although caerulein-induced NF-κB and trypsinogen activation are temporally closely related, they are independent events in pancreatic acinar cells. NF-κB activation per se is not required for the development of early acinar cell injury by supramaximal secretagogue stimulation.

Original languageEnglish (US)
Pages (from-to)388-395
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume280
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Trypsinogen
Ceruletide
Complement Factor B
Rats
Pancreas
Chemical activation
Acinar Cells
Trypsin
Tosyllysine Chloromethyl Ketone
Tosylphenylalanyl Chloromethyl Ketone
Proteasome Inhibitors
Rain
Chymotrypsin
Phorbol Esters
Protease Inhibitors
Pancreatitis
Lipopolysaccharides

Keywords

  • Acinar cell injury
  • Caerulein
  • Digestive enzymes
  • Nuclear factor-κB
  • Pancreas
  • Transcription factor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Relationship between NF-κB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation. / Hietaranta, Antti J.; Saluja, Ashok; Bhagat, Lakshmi; Singh, Vijay P.; Song, Albert M.; Steer, Michael L.

In: Biochemical and Biophysical Research Communications, Vol. 280, No. 1, 01.01.2001, p. 388-395.

Research output: Contribution to journalArticle

Hietaranta, Antti J. ; Saluja, Ashok ; Bhagat, Lakshmi ; Singh, Vijay P. ; Song, Albert M. ; Steer, Michael L. / Relationship between NF-κB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 280, No. 1. pp. 388-395.
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