Inhibition of ubiquitin-activating enzyme protects against organ injury after intestinal ischemia-reperfusion

American Journal of Physiology. Gastrointestinal and Liver Physiology
Shingo MatsuoWeng-Lang Yang

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 the 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 min 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 morphological structure of gut and lung after I/R, as judged by hematoxylin and eosin staining. It also reduced the number of apoptotic terminal deoxynucleotidyl transferase dUTP nick end-labeling-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 keratinocyte chemoattractant and ...Continue Reading

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Citations

Jan 22, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shihong WenWenqi Huang
Apr 10, 2020·Khirurgiia·A I KhripunG A Agasyan

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Methods Mentioned

BETA
ubiquitination
PCR
ELISA
dissection
light microscopy
nuclear translocation

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