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| ROLE OF TRANSGLUTAMINASE AND PROTEIN CROSS-LINKING IN THE REPAIR OF MUCOSAL STRESS EROSIONS |
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| Author(s): WANG JY, JOHNSON LR |
| Source: AMERICAN JOURNAL OF PHYSIOLOGY Volume: 262 Issue: 5 Pages: G818-G825 Part: Part 1 Published: MAY 1992 |
| Times Cited: 31 References: 36 |
| 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. These results indicate that 1) stress-induced gastric and duodenal mucosal erosions are associated with significant increases in transglutaminase activity, 2) induction of enzyme and subsequent protein cross-linking are necessary for mucosal healing, and 3) inhibition of protein cross-linking prevents the effect of polyamines on mucosal healing. The findings suggest that increased transglutaminase and protein cross-linking may be part of the mechanism requiring polyamines for healing of mucosal stress erosions. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV TENNESSEE CTR HLTH SCI, COLL MED, DEPT PHYSIOL & BIOPHYS, NASH RES BLDG, 894 UNION AVE, MEMPHIS, TN 38163 USA |
| Publisher: AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Physiology |
| IDS Number: HV370 |
| ISSN: 0002-9513 |
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