| First Author | Ghouzali I | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1861 |
| Issue | 1 Pt A | Pages | 3278-3288 |
| PubMed ID | 27544233 | Mgi Jnum | J:255431 |
| Mgi Id | MGI:6105203 | Doi | 10.1016/j.bbagen.2016.08.010 |
| Citation | Ghouzali I, et al. (2017) Targeting immunoproteasome and glutamine supplementation prevent intestinal hyperpermeability. Biochim Biophys Acta 1861(1 Pt A):3278-3288 |
| abstractText | BACKGROUND: Intestinal hyperpermeability has been reported in several intestinal and non-intestinal disorders. We aimed to investigate the role of the ubiquitin proteasome system in gut barrier regulation in two mice models: the water avoidance stress model (WAS) and a post-inflammatory model (post-TNBS). METHODS: Both models were applied in C57BL/6 male mice (n=7-8/group); Proteasome was targeted by injection of a selective proteasome inhibitor or by using knock-out mice for beta2i proteasome subunit. Finally, glutamine supplementation was evaluated. RESULTS: In both models (WAS at day 10, post-TNBS at day 28), we observed an increase in proteasome trypsin-like activity and in inducible beta2/constitutive beta2 subunit protein expression ratio, associated with an increase in intestinal permeability. Moreover, intestinal hyperpermeability was blunted by intraperitoneal injection of selective proteasome inhibitor in WAS and post-TNBS mice. Of note, knock-out mice for the beta2i subunit exhibited a significant decrease in intestinal permeability and fecal pellet output during WAS. Glutamine supplementation also improved colonic permeability in both models. CONCLUSIONS: In conclusion, the proteasome system is altered in the colonic mucosa of WAS and post-TNBS mice with increased trypsin-like activity. Associated intestinal hyperpermeability was blunted by immunoproteasome inhibition. |
