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The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or its extract

Abstract

BACKGROUND Cigarette smoking was shown to delay gastric ulcer healing and reduce synthesis of mucus, which is important for gastric ulcer protection and healing. Polyamines are important in these processes.

AIMS To study the effects of cigarette smoking on the synthesis of mucus and to investigate if such an effect is acting by interference with the polyamine pathway.

METHODS Gastric mucosal ornithine decarboxylase activity, mucous secreting layer thickness, and ulcer size were determined after different concentrations of cigarette smoke exposure (0, 2, or 4%) in intact animals and animals with ulcers. Synthesis of mucus and ornithine decarboxylase activity and mRNA expression were also assessed in cigarette smoke extract treated MKN-28 cells.

RESULTS Exposure to cigarette smoke significantly reduced the thickness of the mucous secreting layer and gastric mucosal ornithine decarboxylase activity in animals with or without ulcers. Spermidine not only reversed inhibition of mucus synthesis in both intact and ulcer bearing animals but also reversed the delay in ulcer healing. Cigarette smoke extract significantly reduced mucus synthesis and ornithine decarboxylase activity but not its mRNA expression in MKN-28 cells. The reduction in mucus synthesis was restored by spermidine.

CONCLUSIONS Cigarette smoke and its extract repress mucus synthesis in vivo and in vitro, respectively. Reduction of ornithine decarboxylase activity in gastric mucosa is closely associated with this effect.

  • mucus
  • ornithine decarboxylase
  • cigarette smoking
  • ulcers
  • Abbreviations used in this paper

    DFMO
    DL-α-difluoromethyl-ornithine
    EGF
    epidermal growth factor
    MTT
    3-[4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide
    ODC
    ornithine decarboxylase
    PBS
    phosphate buffered saline;TCA, trichloroacetic acid
    PAS
    periodic acid-Schiff
    RT-PCR
    reverse transcription-polymerase chain reaction
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