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Cell Physiol Biochem. 2014;33(5):1411-25. doi: 10.1159/000358707. Epub 2014 May 5.

Expression of the transcription factor Egr-1 in pancreatic acinar cells following stimulation of cholecystokinin or Gαq-coupled designer receptors.

Author information

1
Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, Homburg, Germany.

Abstract

BACKGOUND/AIMS: The injection of cerulein, an analogue of the pancreatic secretagogue cholecystokinin (CCK), induces acute pancreatitis in mice that is accompanied by the synthesis of the transcription factor Egr-1. The signaling cascade that connects cerulein stimulation with enhanced Egr-1 biosynthesis was analyzed.

METHODS:

AR42J rat pancreatic acinar cells were used as a model system to measure cerulein-induced Egr-1 biosynthesis. For comparison, the signaling cascade induced by activation of Gαq-coupled designer receptors with the designer drug clozapine-N-oxide (CNO) was investigated.

RESULTS:

Stimulation of AR42J cells with cerulein induced a robust and transient biosynthesis of Egr-1. The signaling cascade connecting cerulein stimulation with Egr-1 gene expression required elevated levels of cytosolic Ca(2+) and the activation of the protein kinases PKC, Raf and ERK, while expression of MKP-1 prevented Egr-1 biosynthesis in cerulein-stimulated AR42J cells. In addition, ternary complex factors are required to connect cerulein stimulation with enhanced transcription of the Egr-1 gene. Egr-1 biosynthesis induced in CNO-stimulated AR42J pancreatic acinar cells expressing Gαq-coupled designer receptors required identical signaling molecules, although subtle differences were observed in comparison to cerulein/CCK receptor signaling.

CONCLUSION:

We propose that overstimulation of the canonical Gαq-induced signaling pathway may be crucial for inducing acute pancreatitis.

PMID:
24853800
DOI:
10.1159/000358707
[Indexed for MEDLINE]
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