Induction of EGF-receptor XXXX kinase during early reparative phase of gastric mucosa and effects of aging.

@entity22857 @entity1219 @entity20747 @entity35 @entity12079 @entity669 @entity18696
BACKGROUND: Although the gastric mucosa of adult healthy animals possesses a remarkable capacity to promptly repair its mucosal architecture after an acute injury, aging attenuates this process. We hypothesize that certain @entity669 kinases (Tyr-k), specifically the enzyme associated with EGF-receptor (EGF-R), may play a role in this process. The present investigation was undertaken to evaluate the role of this enzyme in the early reparative phase of the gastric mucosa in young and aged @entity35 . EXPERIMENTAL DESIGN: In our initial effort to test the hypothesis, we examined the changes in both total and EGF-R-associated Tyr-k activities in the gastric mucosa of young adult @entity35 (4-months old) during the first 60 minutes after hypertonic saline (2 M @entity1219 ; 1.5 ml/130 g body weight)-induced injury. Because the maximal stimulation (90-100% over the controls) in both total and EGF-R-associated Tyr-k occurred at 30 minutes after injury, we used this time point to perform the next experiment, in which groups of young and aged @entity35 were given (intragastically) 2 M @entity1219 or water. One of the young and aged groups of @entity35 was also injected (i.p.) with the Tyr-k inhibitor @entity20747 (300 micrograms/kg body weight) 60 minutes before injury. The gastric mucosa was assayed for EGF-R Tyr-k activity and @entity669 phosphorylation and expression of EGF-R, phospholipase C (PLC) activity and relative concentration and @entity669 phosphorylation of @entity22857 , as well as @entity18696 ( @entity18696 ) levels. RESULTS: Basal EGF-R Tyr-k activity and the extent of @entity669 phosphorylation of EGF-R, as well as PLC activity, were all found to be higher in the gastric mucosa of aged than in young @entity35 . Although 30 minutes after injury, EGF-R Tyr-k activity, @entity669 phosphorylation of EGF-R, and relative abundance of the receptor were all increased in the gastric mucosa of both young and aged @entity35 , the magnitude of stimulation of each of the parameters was found to be considerably lower in aged than in young @entity35 , compared with the corresponding basal levels. A similar phenomenon was also observed for PLC activity and @entity669 phosphorylation of @entity22857 . The relative concentration of mucosal @entity22857 level was, however, not affected by injury in either young or aged @entity35 . @entity12079 greatly attenuated the injury-induced increases in the above mentioned parameters in both young and aged @entity35 . In young but not in aged @entity35 , injury caused a significant increase in mucosal @entity18696 levels. CONCLUSIONS: We conclude that (a) activation of EGF-R Tyr-k is an important event in the early reparative process of the gastric mucosa, and (b) local production of @entity18696 may play an important role in regulating the activation of EGF-R Tyr-k.
