Inhibition of Ubiquitin-activating Enzyme Protects against Organ Injury after Intestinal Ischemia-Reperfusion.

Inhibition of Ubiquitin-activating Enzyme Protects against Organ Injury after Intestinal Ischemia-Reperfusion. Am J Physiol Gastrointest Liver Physiol. 2018 May 17;: Authors: Matsuo S, Chaung A, Liou D, Wang P, Yang WL Abstract Intestinal ischemia-reperfusion (I/R) occurs in various clinical settings, such as transplantation, acute mesenteric arterial occlusion, trauma and shock. I/R injury causes severe systemic inflammation, leading to multiple organ dysfunction associated with high mortality. The ubiquitin proteasome pathway has been indicated in the regulation of inflammation, particularly through NF-κB signaling pathway. PYR-41 is a small molecular compound that selectively inhibits ubiquitin-activating enzyme E1. A mouse model of intestinal I/R injury by clamping the superior mesenteric artery for 45 minutes was performed to evaluate the effect of PYR-41 treatment on organ injury and inflammation. PYR-41 was administered intravenously at the beginning of reperfusion. Blood and organ tissues were harvested at 4 h after reperfusion. PYR-41 treatment improved the morphologic structure of gut and lung after I/R, as judged by H&E staining. It also reduced number of apoptotic TUNEL-positive cells and caspase-3 activity in the organs. PYR-41 treatment decreased the expression of proinflammatory cytokines IL-6 and IL-1β as well as chemokines KC and MIP-2 in the gut and lung, which leads to inhibition of neutrophils infiltrating i...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research