title: Regulation of growth and apoptosis of cultured guinea pig gastric mucosal cells by mitogenic oxidase 1.
abstract: We previously reported that primary cultures of guinea pig gastric pit cells expressed all of the phagocyte NADPH oxidase components (gp91-, p22-, p67-, p47-, and p40-phox) and could spontaneously release superoxide anion (O(2)(-)). We demonstrate here that pit cells express a nonphagocyte-specific gp91-phox homolog (Mox1) but not gp91-phox. Inclusion of catalase significantly inhibited [(3)H]thymidine uptake during the initial 2 days of culture. Pit cells, matured on day 2, slowly underwent spontaneous apoptosis. Scavenging O(2)(-) and related oxidants by superoxide dismutase plus catalase or N-acetyl cysteine (NAC) 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(2)F. Mox1-derived reactive oxygen intermediates constitutively activated nuclear factor-kappaB, and inhibition of this activity by nuclear factor-kappaB decoy oligodeoxynucleotide accelerated their spontaneous apoptosis. These results suggest that O(2)(-) produced by the pit cell Mox1 oxidase may play a crucial role in the regulation of their spontaneous apoptosis as well as cell proliferation.
authors.affiliation: Department of Nutrition, School of Medicine, The University of Tokushima, Tokushima City, Tokushima 770-8503, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Teshima
authors.forename: H
authors.initials: H
authors.lastname: Kutsumi
authors.forename: T
authors.initials: T
authors.lastname: Kawahara
authors.forename: K
authors.initials: K
authors.lastname: Kishi
authors.forename: K
authors.initials: K
authors.lastname: Rokutan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000201:enzymology / Q000254:growth & development / Q000502:physiology*; D006168:Guinea Pigs; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019255:NADPH Oxidases; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme; D020169:Caspases