Role of transglutaminase and protein cross-linking in the repair of mucosal stress erosions

Abstract

We have recently demonstrated that polyamines are absolutely required for gastric and duodenal mucosal repair after stress. Polyamines act as substrates for transglutaminase and facilitate protein cross-linking. The current study tests whether transglutaminase and protein cross-linking are involved in the mechanism of mucosal healing. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 6 h. Animals were killed immediately or 4, 12, or 24 h after stress. Gastric and duodenal mucosa were examined histologically and grossly, and transglutaminase activity was measured. Transglutaminase activity in gastric and duodenal mucosa was increased significantly from 0 to 8 h, peaking 4 h after the 6-h stress period. By 12 h, enzyme activity in duodenal mucosa had returned to control values while gastric mucosal transglutaminase did not decrease to control values until 24 h. Mucosal recovery from lesions produced by stress was evident 12 h after stress and was almost complete by 24 h. Dansylcadaverine (100 mg/kg, orally), a specific inhibitor of protein cross-linking, not only prevented the increases in transglutaminase but significantly decreased healing in both tissues. Oral administration of the polyamine spermidine (100 mg/kg) immediately after stress totally prevented inhibition of repair caused by blocking ornithine decarboxylase with difluoromethylornithine (DFMO, 500 mg/kg). Administration of dansylcadaverine, together with spermidine, significantly prevented the beneficial effect of spermidine on mucosal healing in the DFMO-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)