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

• Published in: PloS one Vol. 8; no. 11; p. e81767
• Main Authors: Xu, Ping, Wang, Jing, Yang, Zhi-wen, Lou, Xiao-li, Chen, Cheng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.11.2013; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Acute Disease; AKT protein; Amylases; Amylases - blood; Animals; Apoptosis; Bile; Cytokines; Cytokines - blood; Edema; Gangrene; Gastroenterology; Gene Expression Regulation, Enzymologic; Hemorrhage; Hospitals; Inflammation; Inhibitors; Interleukin 6; Kinases; Laboratory animals; Male; NF-κB protein; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Pancreas; Pancreatitis; 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; Regulatory mechanisms (biology); Rodents; SAP protein; Signal Transduction; Signaling; Sodium; Thermal cycling; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Tumor necrosis factor-α; Wortmannin; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081767

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.