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Related Concept Videos

  • Biomedical And Clinical Sciences
  • Immunology
  • Autoimmunity
  • Role Of The Proteasome In Rat Indomethacin-induced Gastropathy.
  • Biomedical And Clinical Sciences
  • Immunology
  • Autoimmunity
  • Role Of The Proteasome In Rat Indomethacin-induced Gastropathy.

    • Related Experiment Videos

    Role of the proteasome in rat indomethacin-induced gastropathy.

    S J Brand1, Z Morise, S Tagerud

    • 1ProScript Inc., Cambridge, Massachusetts, USA. sbrand@trlusa.com

    Gastroenterology
    |March 26, 1999

    View abstract on PubMed

    Summary
    This summary is machine-generated.

    Proteasome inhibitors effectively prevent nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy by blocking intercellular adhesion molecule (ICAM) expression. This study demonstrates the therapeutic potential of proteasome inhibition in mitigating NSAID-related gastrointestinal damage.

    Related Experiment Videos

    Area of Science:

    • Gastroenterology
    • Pharmacology
    • Cell Biology

    Background:

    • Nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy involves intercellular adhesion molecule (ICAM)-dependent neutrophil adhesion.
    • Indomethacin elevates tumor necrosis factor (TNF)-alpha, increasing ICAM expression on gastric endothelial cells.
    • ICAM expression is regulated by NF-kappaB activation, which depends on the ubiquitin-proteasome pathway.

    Purpose of the Study:

    • To evaluate the efficacy of proteasome inhibitors in preventing NSAID-induced gastropathy.
    • To assess the impact of proteasome inhibitors on gastric mucosal permeability and ICAM expression.

    Main Methods:

    • Gastric injury and mucosal permeability (EDTA clearance) were measured after indomethacin administration with proteasome inhibitors.
    • Gastric endothelial ICAM expression was quantified in vivo using a labeled ICAM antibody.
    • Different classes of proteasome inhibitors (peptide boronates, aldehydes, lactacystin) were tested.

    Main Results:

    • Proteasome inhibitors administered before indomethacin significantly prevented gastropathy.
    • Both oral and intravenous proteasome inhibitor administration showed equivalent efficacy.
    • Inhibitors reduced gastric mucosal permeability and indomethacin-induced increases in gastric endothelial ICAM expression.

    Conclusions:

    • Inhibition of the proteasome pathway effectively prevents indomethacin-induced gastric injury.
    • Proteasome inhibitors reduce gastric mucosal permeability and ICAM expression associated with NSAID use.