{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:15:33Z","timestamp":1789539333060,"version":"build-2803163510"},"reference-count":78,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T00:00:00Z","timestamp":1476662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["K01AA022979\u201001"],"award-info":[{"award-number":["K01AA022979\u201001"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp; Exp Res"],"published-print":{"date-parts":[[2016,12]]},"abstract":"Background<\/jats:title>It is known that ethanol (EtOH) and its metabolites have a negative effect on protein glycosylation. The fragmentation of the Golgi apparatus induced by alteration of the structure of largest Golgi matrix protein, giantin, is the major consequence of damaging effects of EtOH<\/jats:styled-content>\u2010metabolism on the Golgi; however, the link between this and abnormal glycosylation remains unknown. Because previously we have shown that Golgi morphology dictates glycosylation, we examined the effect EtOH<\/jats:styled-content> administration has on function of Golgi residential enzymes involved in N<\/jats:italic>\u2010glycosylation.<\/jats:p><\/jats:sec>Methods<\/jats:title>HepG2 cells transfected with mouse ADH<\/jats:styled-content>1 (VA<\/jats:styled-content>\u201013 cells) were treated with 35\u00a0mM<\/jats:styled-content> EtOH for 72\u00a0hours. Male Wistar rats were pair\u2010fed Lieber\u2010DeCarli diets for 5 to 8\u00a0weeks. Characterization of Golgi\u2010associated mannosyl (\u03b1<\/jats:italic>\u20101,3\u2010)\u2010glycoprotein beta\u20101,2\u2010N<\/jats:italic>\u2010acetylglucosaminyltransferase (MGAT<\/jats:styled-content>1), \u03b1<\/jats:italic>\u20101,2\u2010mannosidase (Man\u2010I), and \u03b1<\/jats:italic>\u2010mannosidase II<\/jats:styled-content> (Man\u2010II<\/jats:styled-content>) were performed in VA<\/jats:styled-content>\u201013 cells and rat hepatocytes followed by three\u2010dimensional structured illumination microscopy (3D SIM<\/jats:styled-content>).<\/jats:p><\/jats:sec>Results<\/jats:title>First, we detected that EtOH<\/jats:styled-content> administration results in the loss of sialylated N<\/jats:italic>\u2010glycans on asialoglycoprotein receptor; however, the high\u2010mannose\u2010type N<\/jats:italic>\u2010glycans are increased. Further analysis by 3D SIM<\/jats:styled-content> revealed that EtOH<\/jats:styled-content> treatment despite Golgi disorganization does not change cis<\/jats:italic>\u2010Golgi localization for Man\u2010I, but does induce medial<\/jats:italic>\u2010to\u2010cis<\/jats:italic> relocation of MGAT<\/jats:styled-content>1 and Man\u2010II<\/jats:styled-content>. Using different approaches, including electron microscopy, we revealed that EtOH<\/jats:styled-content> treatment results in dysfunction of ADP\u2010ribosylation factor 1 (Arf1) GTP<\/jats:styled-content>ase followed by a deficiency in COPI<\/jats:styled-content> vesicles at the Golgi. Silencing beta\u2010COP<\/jats:styled-content> or expression of GDP<\/jats:styled-content>\u2010bound mutant Arf1(T31N) mimics the EtOH<\/jats:styled-content> effect on retaining MGAT<\/jats:styled-content>1 and Man\u2010II<\/jats:styled-content> at the cis<\/jats:italic>\u2010Golgi, suggesting that (i) EtOH<\/jats:styled-content> specifically blocks activation of Arf1, and (ii) EtOH<\/jats:styled-content> alters the proper localization of Golgi enzymes through impairment of COPI<\/jats:styled-content>. Importantly, the level of MGAT<\/jats:styled-content>1 was reduced, because likely MGAT<\/jats:styled-content>1, contrary to Man\u2010I and Man\u2010II<\/jats:styled-content>, is giantin sensitive.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Thus, we provide the mechanism by which EtOH<\/jats:styled-content>\u2010induced Golgi remodeling may significantly modify formation of N<\/jats:italic>\u2010glycans.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13247","type":"journal-article","created":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T14:39:17Z","timestamp":1476715157000},"page":"2573-2590","source":"Crossref","is-referenced-by-count":21,"title":["Study of Ethanol\u2010Induced Golgi Disorganization Reveals the Potential Mechanism of Alcohol\u2010Impaired N<\/i>\u2010Glycosylation"],"prefix":"10.1111","volume":"40","author":[{"given":"Carol A.","family":"Casey","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Nebraska Medical Center and 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