{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T19:29:49Z","timestamp":1772738989182,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"publisher","award":["31771992"],"award-info":[{"award-number":["31771992"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>N-glycolylneuraminic acid (Neu5Gc) is a specific factor in red meat that induces intestinal disease. Our aim was to investigate the effect of Neu5Gc on the intestinal barrier as well as its mechanism of endocytosis and exocytosis. Ten specific inhibitors were used to explore the mechanism of Neu5Gc endocytosis and exocytosis by Caco-2 cells. Amiloride hydrochloride and cytochalasin D had the strongest inhibitory effect on the endocytosis of Neu5Gc. Sodium azide, dynasore, chlorpromazine hydrochloride, and nystatin also inhibited Neu5Gc endocytosis. Dynasore exhibited a stronger inhibitory effect than that of chlorpromazine hydrochloride or nystatin alone. Exocytosis inhibitors, including nocodazole, brefeldin A, monensin, and bafilomycin A, inhibited the transmembrane transport of Neu5Gc. Monensin promoted the exocytosis of Neu5Gc from Caco-2 cells. In another experiment, we observed no significant inhibitory effects of monensin and brefeldin A. Dietary concentrations of Neu5Gc induced prominent damage to intestinal tight junction proteins zonula occludens-1 (ZO-1), occludin, and claudin-1 and promoted the phosphorylation of I\u03baB-\u03b1 and P65 to activate the canonical Nuclear Factor kappa-B (NF-\u03baB) pathway. Neu5Gc increased the RNA levels of pro-inflammatory factors IL-1\u03b2, IL-6, and TNF-\u03b1 and inhibited those of anti-inflammatory factors TGF-\u03b2 and IL-10. BAY, an NF-\u03baB signaling pathway inhibitor, attenuated these changes. Reductions in the levels of ZO-1, occludin, and claudin-1 were recovered in response to BAY. Our data reveal the endocytosis and exocytosis mechanism of Neu5Gc and prove that Neu5Gc can activate the canonical NF-\u03baB signaling pathway, regulate the transcription of inflammatory factors, thereby damaging intestinal barrier function.<\/jats:p>","DOI":"10.3390\/toxins15020132","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T01:35:17Z","timestamp":1675733717000},"page":"132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Absorption and Transport Mechanism of Red Meat-Derived N-glycolylneuraminic Acid and Its Damage to Intestinal Barrier Function through the NF-\u03baB Signaling Pathway"],"prefix":"10.3390","volume":"15","author":[{"given":"Enqi","family":"He","sequence":"first","affiliation":[{"name":"School of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8305-2778","authenticated-orcid":false,"given":"Wei","family":"Quan","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7291-0933","authenticated-orcid":false,"given":"Jie","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuxin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanting","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwu","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1001\/archinternmed.2011.2287","article-title":"Red Meat Consumption and Mortality: Results from 2 Prospective Cohort Studies","volume":"172","author":"Pan","year":"2012","journal-title":"Arch. 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