{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:45:11Z","timestamp":1784396711887,"version":"3.55.0"},"reference-count":54,"publisher":"Portland Press Ltd.","issue":"8","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4,25]]},"abstract":"<jats:p>Intestinal epithelial oxidative stress and apoptosis constitute key pathogenic mechanisms underlying intestinal ischemia\/reperfusion (I\/R) injury. We previously reported that the adaptor 66\u00a0kDa isoform of the adaptor molecule ShcA (p66Shc)-mediated pro-apoptotic pathway was activated after intestinal I\/R. However, the upstream regulators of the p66Shc pathway involved in intestinal I\/R remain to be fully identified. Here, we focused on the role of a prolyl-isomerase, peptidyl\u2013prolyl cis\u2013trans isomerase (Pin1), in the regulation of p66Shc activity during intestinal I\/R. Intestinal I\/R was induced in rats by superior mesenteric artery (SMA) occlusion. Juglone (Pin1 inhibitor) or vehicle was injected intraperitoneally before I\/R challenge. Caco-2 cells were exposed to hypoxia\/reoxygenation (H\/R) in\u00a0vitro to simulate an in\u00a0vivo I\/R model. We found that p66Shc was significantly up-regulated in the I\/R intestine and that this up-regulation resulted in the accumulation of intestinal mitochondrial reactive oxygen species (ROS) and massive epithelial apoptosis. Moreover, intestinal I\/R resulted in elevated protein expression and enzyme activity of Pin1 as well as increased interaction between Pin1 and p66Shc. This Pin1 activation was responsible for the translocation of p66Shc to the mitochondria during intestinal I\/R, as Pin1 suppression by juglone or siRNA markedly blunted p66Shc mitochondrial translocation and the subsequent ROS generation and cellular apoptosis. Additionally, Pin1 inhibition alleviated gut damage and secondary lung injury, leading to improvement of survival after I\/R. Collectively, our findings demonstrate for the first time that Pin1 inhibition protects against intestinal I\/R injury, which could be partially attributed to the p66Shc-mediated mitochondrial apoptosis pathway. This may represent a novel prophylactic target for intestinal I\/R injury.<\/jats:p>","DOI":"10.1042\/cs20160799","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T01:31:11Z","timestamp":1487899871000},"page":"759-773","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Inhibition of p66Shc-mediated mitochondrial apoptosis via targeting prolyl-isomerase Pin1 attenuates intestinal ischemia\/reperfusion injury in rats"],"prefix":"10.1042","volume":"131","author":[{"given":"Dongcheng","family":"Feng","sequence":"first","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Zu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuwen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shili","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Qasim","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2017,4,6]]},"reference":[{"key":"2021113011074619900_B1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1053\/j.tvir.2014.12.004","article-title":"Acute mesenteric ischemia","volume":"18","author":"Stone","year":"2015","journal-title":"Tech. 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