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Hydrogen peroxide contributes to motor dysfunction in ulcerative colitis.

Weibiao Cao1, Matthew D Vrees, Michael T Kirber

  • 1Dept. of Medicine, Brown Medical School and Rhode Island Hospital, 593 Eddy St., SWP-510, Providence, RI 02903, USA. Weibiao_Cao@brown.edu

American Journal of Physiology. Gastrointestinal and Liver Physiology
|December 13, 2003
PubMed
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Hydrogen peroxide (H2O2) contributes to colonic motor dysfunction in ulcerative colitis (UC) by reducing neurokinin A (NKA)-induced calcium release in muscle cells, impacting gut motility.

Area of Science:

  • Gastroenterology
  • Cellular Physiology
  • Molecular Pharmacology

Background:

  • Ulcerative colitis (UC) impairs colonic motor function through incompletely understood mechanisms.
  • Neurokinin A (NKA) is identified as a potential neurotransmitter mediating contraction in human sigmoid colonic circular muscle (HSCCM).

Purpose of the Study:

  • To investigate the role of hydrogen peroxide (H2O2) in the diminished NKA-induced response observed in HSCCM from UC patients.
  • To elucidate the cellular mechanisms underlying UC-associated colonic dysmotility.

Main Methods:

  • Comparison of NKA-induced contraction and intracellular calcium (Ca2+) signaling in normal and UC HSCCM.
  • Assessment of Ca2+ release from intracellular stores using Ca2+-free medium (CFM) and BAPTA.
  • Evaluation of H2O2 involvement using catalase (an H2O2 scavenger) and direct H2O2 treatment of normal cells.

Related Experiment Videos

  • Measurement of H2O2 levels in normal and UC HSCCM.

    • Main Results:

    • UC muscle cells exhibited reduced NKA-induced Ca2+ release and contraction, particularly in CFM, indicating impaired intracellular Ca2+ release.
    • H2O2 scavenger catalase partially restored NKA-induced Ca2+ signaling and contraction in UC cells.
    • Elevated H2O2 levels were detected in UC HSCCM compared to normal tissue.
    • H2O2 treatment of normal cells mimicked the UC-related reduction in NKA-induced Ca2+ release and directly triggered Ca2+ release from intracellular stores.

    Conclusions:

    • Hydrogen peroxide (H2O2) likely contributes to the reduced NKA-induced Ca2+ release from intracellular stores in ulcerative colitis.
    • Increased H2O2 levels in UC may be a key factor in the colonic motor dysfunction observed in the condition.