{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:32:35Z","timestamp":1768966355738,"version":"3.49.0"},"reference-count":50,"publisher":"American Physiological Society","issue":"2","funder":[{"name":"US National Institute of Health","award":["R35GM118337"],"award-info":[{"award-number":["R35GM118337"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:p>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-\u03baB 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-1\u03b2 as well as chemokines keratinocyte chemoattractant and macrophage inflammatory protein-2 in the gut and lung, which leads to inhibition of neutrophils infiltrating into these organs. The serum levels of IL-6, aspartate aminotransferase, and lactate dehydrogenase were reduced by the treatment. The I\u03baB degradation in the gut increased after I\/R was inhibited by PYR-41 treatment. Thus, ubiquitination may be a potential therapeutic target for treating patients suffering from intestinal I\/R.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Excessive inflammation contributes to organ injury from intestinal ischemia-reperfusion (I\/R) in many clinical conditions. NF-\u03baB signaling is very important in regulating inflammatory response. In an experimental model of gut I\/R injury, we demonstrate that administration of a pharmacological inhibitor of ubiquitination process attenuates NF-\u03baB activation, leading to reduction of inflammation, tissue damage, and apoptosis in the gut and lungs. Therefore, ubiquitination process may serve as a therapeutic target for treating patients with intestinal I\/R injury.<\/jats:p>","DOI":"10.1152\/ajpgi.00024.2018","type":"journal-article","created":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T18:51:30Z","timestamp":1526583090000},"page":"G283-G292","source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of ubiquitin-activating enzyme protects against organ injury after intestinal ischemia-reperfusion"],"prefix":"10.1152","volume":"315","author":[{"given":"Shingo","family":"Matsuo","sequence":"first","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Chaung","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanna","family":"Liou","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York"},{"name":"Department of Surgery, Zucker School of Medicine at Hofstra\/Northwell, Hempstead, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-6557","authenticated-orcid":false,"given":"Weng-Lang","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Manhasset, New York"},{"name":"Department of Surgery, Zucker School of Medicine at Hofstra\/Northwell, Hempstead, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000057843.47705.E8"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semvascsurg.2009.12.001"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318193e333"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines5030050"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.03.033"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13627"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2013.08.006"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200804-625OC"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.081507.101607"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000000631"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.02.006"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091069"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-200115010-00001"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.120"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90576.2008"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03872.x"},{"key":"B17","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0022-3565(24)29408-8","volume":"298","author":"Itoh M","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2741\/2853"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060310-170328"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/00075198-200102000-00001"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0b013e32835ef1eb"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2174\/1389450003349056"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1023\/B:DDAS.0000042232.98927.91"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000000329"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000931"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nature07201"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000278497.47041.e3"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000071060.78689.f1"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2056"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-083012-130338"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2005.06.002"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00177.2010"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2012.03.011"},{"key":"B35","first-page":"574","volume":"107","author":"Park PO","year":"1990","journal-title":"Surgery"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1986.250.6.G749"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2613.2006.00490.x"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2016.08.006"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/BF00914095"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2174\/138161211796390994"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.6.4137"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11830"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.06.027"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1177\/1087057111433843"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-231191"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122214"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0568"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-004-2924-0"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00654.2012"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.12.012"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00024.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T16:14:19Z","timestamp":1751645659000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00024.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,1]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,8,1]]}},"alternative-id":["10.1152\/ajpgi.00024.2018"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00024.2018","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,1]]}}}