title: A nuclear import inhibitory peptide ameliorates the severity of cholecystokinin-induced acute pancreatitis.
abstract: OBJECTIVE
  To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-kappaB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-kappaB p50 subunit.
  
  
  METHODS
  Pancreatitis was induced in male Wistar rats by administering 2X100 mug/kg body weight of cholecystokinin-octapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.
  
  
  RESULTS
  All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity, pancreatic levels of TNF-alpha and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-kappaB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide. According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.
  
  
  CONCLUSIONS
  Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-kappaB might be clinically useful for the suppression of the severity of acute pancreatitis.
authors.affiliation: Department of Medical Chemistry, University of Szeged, Domter 8, H-6720 Szeged, Hungary. tletoha@yahoo.com
authors.forename: Tamas
authors.initials: T
authors.lastname: Letoha
authors.forename: Csaba
authors.initials: C
authors.lastname: Somlai
authors.forename: Tamas
authors.initials: T
authors.lastname: Takacs
authors.forename: Annamaria
authors.initials: A
authors.lastname: Szabolcs
authors.forename: Katalin
authors.initials: K
authors.lastname: Jarmay
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Rakonczay
authors.forename: Peter
authors.initials: P
authors.lastname: Hegyi
authors.forename: Ilona
authors.initials: I
authors.lastname: Varga
authors.forename: Jozsef
authors.initials: J
authors.lastname: Kaszaki
authors.forename: Istvan
authors.initials: I
authors.lastname: Krizbai
authors.forename: Imre
authors.initials: I
authors.lastname: Boros
authors.forename: Erno
authors.initials: E
authors.lastname: Duda
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Kusz
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
mesh_terms: D021581:Active Transport, Cell Nucleus; D000208:Acute Disease; D000595:Amino Acid Sequence; D000681:Amylases / Q000097:blood; D000818:Animals; D001835:Body Weight; D002461:Cell Line, Transformed; D024202:Electrophoretic Mobility Shift Assay; D005978:Glutathione / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D010455:Peptides / Q000235:genetics / Q000493:pharmacokinetics*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D000681:Amylases; D005978:Glutathione; D012844:Sincalide
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