Letoha T, Fehér LZ, Pecze L, Somlai C, Varga I, Kaszaki J, Tóth G, Vizler C, Tiszlavicz L, Takács T. Therapeutic proteasome inhibition in experimental acute pancreatitis. World J Gastroenterol 2007; 13(33): 4452-4457 [PMID: 17724800 DOI: 10.3748/wjg.v13.i33.4452]
Corresponding Author of This Article
Dr. Tamás Letoha, Department of Medical Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary. tletoha@yahoo.com
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Basic Research
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World J Gastroenterol. Sep 7, 2007; 13(33): 4452-4457 Published online Sep 7, 2007. doi: 10.3748/wjg.v13.i33.4452
Therapeutic proteasome inhibition in experimental acute pancreatitis
Tamás Letoha, Liliána Z Fehér, László Pecze, Csaba Somlai, Ilona Varga, József Kaszaki, Gábor Tóth, Csaba Vizler, László Tiszlavicz, Tamás Takács
Tamás Letoha, Csaba Somlai, Gábor Tóth, Department of Medical Chemistry, University of Szeged, H-6720 Szeged, Hungary
Liliána Z Fehér, László Pecze, Csaba Vizler, Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, H-6726 Szeged, Hungary
Ilona Varga, Department of Genetics and Molecular Biology, University of Szeged, H-6726 Szeged, Hungary
József Kaszaki, Institute of Surgical Research, University of Szeged, H-6720 Szeged, Hungary
László Tiszlavicz, Department of Pathology, University of Szeged, H-6720 Szeged, Hungary
Tamás Takács, First Department of Medicine, University of Szeged, H-6720 Szeged, Hungary
Author contributions: All authors contributed equally to the work.
Supported by the postdoctoral fellowship of the Hungarian Ministry of Education and the National Research Foundations (OTKA) grants T30735, T042589 and TS049817
Correspondence to: Dr. Tamás Letoha, Department of Medical Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary. tletoha@yahoo.com
Telephone: +36-62-545136 Fax: +36-62-545971
Received: May 5, 2007 Revised: May 23, 2007 Accepted: May 28, 2007 Published online: September 7, 2007
Abstract
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.
