ROLE OF APOPTOSIS IN GASTRIC MUCOSAL ATROPHY INDUCED BY HELICOBACTER PYLORI INFECTION

点击翻译按钮获取中文摘要

Induction of apoptosis by Helicobacter pylori (H.pylori) infection has been reported in patients with chronic atrophic gastritis. Many investigators have reported that reactive oxygen and nitrogen species, especially H_2O_2, HClO, NH_2Cl, and NO are involved in the pathogenesis of gastric mucosal injuries. However, it is unclear whether these species affect the growth of gastric epithelial cells, or what the mode of action might be for any such changes in proliferation and apoptosis. In this project, the effects of these reactive species on mucosal cell growth and the cell cycle were evaluated in vitro using a normal rat gastric mucosal cell line RGM-1. H_2O_2, HClO, NH_2Cl, and NO exerted a dose-dependent inhibition of RGM-1 cell growth at 0.1 - 100 muM.Exposure of cells to NH_2Cl and NO caused a time- and dose- dependent loss of G1-phase cells with accumulation of G2/M phase cells, and produced a fraction of subdiploid cells with oligonucleosomal DNA degradation characteristic of apoptosis. NH_2Cl- and NO-induced apoptosis was confirmed by fluorescent microscopy with Hoechst 33342 and propidium iodide. NO treatment also induced 1) the decrease in glutathione content, 2) the increase in inrtracellular reactive oxygen production, and 3) the formation of 8-OH- deoxyguanosine. These results suggest that NH_2Cl and NO inhibits gastric mucosal cell growth, and induces apoptosis in RGM-1 cells, events which may be important in gastric mucosal damage or atrophy induced by H.pylori infection. As a candidate possessing inhibitory properties against these oxidative gastric mucosal cell, we evaluated the effects of a novel water-soluble vitamin E analogue and natural functional foods.