Production of superoxide anion and its physiological roles in gastric mucosal cells

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We demonstrated that primary cultures of guinea pig gastric pit cells expressed all of the phagocyte NADPH oxidase components (p22-, p67-, p47-, and p40-phoxes) and could spontaneously release superoxide anion. We also identified that pit cells express a nonphagocyte-specific gp91-phox homolog (Mox1), but not gp91-phox. Lipopolysaccharide from Helico bacter pylori markedly enhanced the Mox1 oxidase activity. Inclusion of catalase significantly inhibited pit cell growth. Scavenging superoxide anion and related oxidants by superoxide dismutase plus catalase or N-acetyl cysteine and inhibiting Mox1 oxidase by diphenylene iodonium activated caspase 3-like proteases and markedly enhanced chromatin condensation and DNA fragmentation. This accelerated apoptosis was completely blocked by a caspase inhibitor, z-Val-Ala-Asp-CH_2F.Mox1-derived reactive oxygen intermediates constitutively activated nuclear factor kB (NF-kB), and inhibition of this activity by NF-kB decoy oligodeoxynucleotide accelerated their spontaneous apoptosis. These results suggest that superoxide anion produced by the pit cell Mox1 oxidase may play a crucial role in the regulation of their spontaneous apoptosis as well as cell proliferation.