Expression of the transcription factor Egr-1 in pancreatic acinar cells following stimulation of cholecystokinin or Gαq-coupled designer receptors.
Anke Kaufmann, Oliver G Rössler, Gerald Thiel
文献索引:Cell Physiol. Biochem. 33(5) , 1411-25, (2014)
全文:HTML全文
摘要
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.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.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.We propose that overstimulation of the canonical Gαq-induced signaling pathway may be crucial for inducing acute pancreatitis.© 2014 S. Karger AG, Basel.
相关化合物
相关文献:
2015-11-01
[Br. J. Pharmacol. 172 , 5050-67, (2015)]
1995-01-01
[Peptides 16(7) , 1229-34, (1995)]
2005-08-05
[Biochem. Biophys. Res. Commun. 333(3) , 778-86, (2005)]
1987-11-01
[Arzneimittelforschung 37 , 1265-1268, (1987)]
1991-02-01
[Br. J. Pharmacol. 102 , 391-395, (1991)]