title: Autophagy regulation by the nuclear factor κB signal axis in acute pancreatitis.
abstract: OBJECTIVE
  The objective of the study was to investigate the significance of LC3 and beclin 1 in the pancreas of rat after acute necrotizing pancreatitis (ANP) and whether nuclear factor κB (NF-κB) signal regulates autophagy during sodium taurocholate-induced ANP.
  
  
  METHODS
  Acute necrotizing pancreatitis was induced in rat by sodium taurocholate injection in the pancreaticobiliary duct. Pyrrolidine dithiocarbamate was administrated before the injection of sodium taurocholate. Then, serum amylase activity, trypsinogen activation peptide and tumor necrosis factor α, and morphological signs of pancreatitis were measured. The formation of autophagosome and the activation of lysosome were observed in the pancreas after ANP by using electron microscope. Meanwhile, the pancreatic levels of NF-κB and essential proteins involved in formation of the autophagosome (LC3 and beclin 1) were assessed by Western blotting and immunohistochemistry.
  
  
  RESULTS
  Sodium taurocholate increased serum amylase, trypsinogen activation peptide, tumor necrosis factor α, and pancreatic NF-κB levels compared with sham-operated rats and increased the levels of LC3-II and beclin 1. Inhibition of the NF-κB signal axis with pyrrolidine dithiocarbamate reduced serum amylase, blocked pancreatic NF-κB activation, and reduced the levels of LC3-II and beclin 1.
  
  
  CONCLUSIONS
  Nuclear factor κB pathway activation stimulates autophagy during induction of ANP. Targeted inhibition of the NF-κB pathway may provide novel therapeutic strategies for reducing the severity of ANP.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Yang
authors.forename: Men
authors.initials: M
authors.lastname: Bing
authors.forename: Fengmei
authors.initials: F
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Huang
authors.initials: H
authors.lastname: Chen
authors.forename: Weichang
authors.initials: W
authors.lastname: Chen
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009842:Oligopeptides / Q000097:blood; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013656:Taurocholic Acid; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000681:Amylases; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009842:Oligopeptides; D011759:Pyrrolidines; D013656:Taurocholic Acid; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C080396:trypsinogen activation peptide; C020972:pyrrolidine dithiocarbamic acid