Regulatory roles of the PI3K/Akt signaling pathway in rats with severe acute pancreatitis

PLoS One. 2013 Nov 28;8(11):e81767. doi: 10.1371/journal.pone.0081767. eCollection 2013.

Abstract

The phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) pathway plays a key role in inflammation. However, the regulatory roles of PI3K/Akt in severe acute pancreatitis (SAP) have not been elucidated. The aim of this study was to investigate the impact of wortmannin, a PI3K/Akt inhibitor, on SAP rats through exposure to sodium taurocholate (STC) after 3 h and 6 h. The SAP group was found to have a significant increase in pancreas Akt expression, along with the activation of serum amylase, TNF-α, IL-1β, and IL-6, and pancreas histological aggravation. The administration of wortmannin in SAP rats reduced Akt expression, attenuated the level of serum amylase and inflammation factor, and alleviated the damage of pancreatic tissue. Furthermore, the administration of wortmannin led to an obvious reduction in NF-κB and p38MAPK expression in SAP rats. These findings showed that the PI3K/Akt inhibitor wortmannin decreases inflammatory cytokines in SAP rats and suggests its regulatory mechanisms may occur through the suppression on NF-κB and p38MAPK activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Amylases / blood
  • Animals
  • Cytokines / blood
  • Gene Expression Regulation, Enzymologic
  • Male
  • Pancreatitis / blood
  • Pancreatitis / genetics
  • Pancreatitis / metabolism*
  • Pancreatitis / pathology*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Cytokines
  • Phosphoproteins
  • Rela protein, rat
  • Transcription Factor RelA
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases
  • Amylases

Grants and funding

The study was supported by a grant from Shanghai Songjiang District Health Board leading cooperative project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.