Effect of gastric mucosal injury on ornithine decarboxylase in young and aged rats.

The present investigation examines the changes in ornithine decarboxylase (ODC) activity, level of the enzyme, and the expression of its gene in gastric mucosa of young (4-month) and aged (24-month) Fischer-344 male rats 6 h after intragastric administration of either 2 M NaCl (1 ml/130 g b.w.) or an equivalent volume of water (controls). In addition, electronmicroscopy was performed to evaluate the ultrastructural changes in the gastric mucosa. Although administration of 2 M NaCl virtually eliminated the surface epithelium in both young and aged rats, the extent to injury in older animals extended beyond the surface epithelium. In aged rats, epithelial cells in the deeper parts of the gastric glands demonstrated severe swelling with vacuolization and disintegration of the cell organelles, with dying and dead cells. Basal gastric mucosal ODC activity (data from the controls) in aged rats was found to be 118% (p less than 0.001) above the young animals. This was also associated with similar increases in the concentration of ODC (as determined by Western-blot analysis) and a steady-state rise in ODC mRNA. Intragastric administration of 2 M NaCl (which caused gastric mucosal injury) resulted in a 625% increase in mucosal ODC activity in young rats, but in aged rats it produced a 112% increase when compared with the corresponding controls. In young rats, the increase in gastric mucosal ODC activity after injury was also associated with about a 2-fold rise in the enzyme protein concentration and a 4-fold increase in steady-state ODC mRNA levels. In contrast, gastric mucosal injury in aged rats, which resulted in a 112% increase in ODC activity, produced about a 30% reduction in the concentration of ODC and a 15-20% reduction in steady-state mRNA levels, when compared with the respective controls. The current data demonstrate that aging is associated with decreased responsiveness of gastric mucosal ODC to injury which may in part be responsible for diminished regenerative capacity of the gastric mucosa in aged animals. Furthermore, in aged rats the injury-induced stimulation of mucosal ODC activity is not associated with increased activation of its gene.