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Regulation of Transglutaminase Activity by Polyamines in the Gastrointestinal Mucosa of Rats

Abstract Transglutaminases catalyze the covalent cross-linking of protein and are involved in the mechanism of polyamine-dependent mucosal healing. The current study examined the effect of polyamines on transglutaminase activity in gastrointestinal mucosa. Rats were fasted 22 hr before experiments and enzyme activity was measured as the Ca++-dependent covalent incorporation of [3H]-putrescine into acid-precipitable protein. In some of the experiments, mucosal ornithine decarboxylase (ODC) activity and polyamine levels were also examined. Transglutaminase activity in both gastric and duodenal mucosa increased significantly after polyamine administration. Treatment with α-difluoromethylornithine (DFMO) decreased both basal ODC activity and putrescine levels in the duodenal mucosa. DFMO also significantly decreased mucosal transglutaminase activity. In stress or hypertonic NaCl-induced gastric mucosal injury models, increased polyamine biosynthesis was associated with increased transglutaminase activity, which was completely prevented by DFMO. Exogenous polyamines returned transglutaminase activity toward control levels in the presence of DFMO. In conclusion, these results indicate that: (i) luminal polyamines increase transglutaminase activity in gastric and duodenal mucosa; (ii) polyamine depletion caused by the inhibition of ODC is accompanied by a significant decrease in transglutaminase activity; and (iii) exogenous polyamines significantly reverse the decrease in transglutaminase activity caused by polyamine depletion.