Role for mucous glycoprotein in protecting cultured rat gastric mucosal cells against toxic oxygen metabolites.
The gastric epithelium is exposed to oxygen radicals that are generated within the lumen. Much interest has been focused on the role of mucus in maintaining integrity of the gastric mucosa against oxidants, because gastric mucus may act as a scavenger of oxygen radicals. The aim of this study was to assess the role of mucous glycoprotein in protecting cultured gastric epithelial cells against oxygen radicals. Monolayer cultures of rat gastric mucus-producing cells were studied. Oxygen radicals were generated by hypoxanthine and xanthine oxidase. Cytotoxicity was quantified by measuring chromium 51 release form prelabeled cells. Rate of mucous synthesis was estimated by incorporation of tritiated glucosamine into the cells. The effects of tetraprenyl acetone (a stimulant of mucus production) and N-acetyl-L-cysteine (a mucolytic agent) on oxygen radical-induced damage were determined. Preincubation with tetrapenyl acetone, while stimulating mucous glycoprotein by the cultured cells, caused a dose-dependent reduction of hypoxanthine-xanthine oxidase-induced 51Cr release, reaching maximum protection of the damage by 31% to 50%. In contrast, pretreatment with N-acetyl-L-cysteine potentiated oxygen radical-induced 51Cr release dose dependently. The protective effect of tetraprenyl acetone was significantly abolished by N-acetyl-L-cysteine. Neither tetraprenyl acetone nor N-acetyl-L-cysteine alone under the conditions of this study affected the cellular content of glutathione, which modulates oxygen radical injury to these cells. These results suggest that mucous glycoprotein partially but significantly protects cultured gastric epithelial cells against extracellularly generated oxygen radicals. It seems likely, therefore, that gastric mucus is involved in antioxidant defenses in these cells.
Hiraishi
H
H
Department of Medicine, Veterans Affairs Medical Center, Long Beach, CA 90822.
Terano
A
A
Ota
S
S
Mutoh
H
H
Sugimoto
T
T
Harada
T
T
Razandi
M
M
Ivey
K J
KJ
D000111:Acetylcysteine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005978:Glutathione / Q000032:analysis; D006023:Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000378:metabolism
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D006023:Glycoproteins; C047874:gastric mucus glycoproteins; D014969:Xanthine Oxidase; D005978:Glutathione; D010100:Oxygen; C031049:geranylgeranylacetone; D000111:Acetylcysteine