Therapeutic proteasome inhibition in experimental acute pancreatitis

• 作 者: Tamás Letoha Liliána Z Fehér László Pecze Csaba Somlai Ilona Varga József Kaszaki Gábor Tóth Csaba Vizier László Tiszlavicz Tamás Takács
• 机 构: Department of Medical Chemistry, University of Szeged, H-6720 Szeged,Hungary“,”Institute of Biochemi
• 出 处: 世界胃肠病学杂志（英文版）
• 发表日期: 2007年33期
• 关键词: Acute pancreatitis Cholecystokinin octapeptide Proteasome inhibition Nuclear fac

AIM: To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis.METHODS: Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2 × 100 μg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK.RESULTS: Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-κB (NF-κB).Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress.CONCLUSION: Our findings suggest that proteasome inhibition might be beneficial not only for the prevention,but also for the therapy of acute pancreatitis.