{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T05:44:20Z","timestamp":1696571060812},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,1,31]],"date-time":"2014-01-31T00:00:00Z","timestamp":1391126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp; Exp Res"],"published-print":{"date-parts":[[2014,3]]},"abstract":"Background<\/jats:title>Protein kinase C epsilon (PKC<\/jats:styled-content>\u03b5<\/jats:italic>) has been shown to play a role in experimental steatosis by acute alcohol. The \u201ctwo\u2010hit\u201d hypothesis implies that preventing steatosis should blunt more advanced liver damage (e.g., inflammation and necrosis). However, the role of PKC<\/jats:styled-content>\u03b5<\/jats:italic> in these pathologies is not yet known. The goal of this current work was to address this question in a model of chronic alcohol exposure using antisense oligonucleotides (ASO<\/jats:styled-content>) against PKC<\/jats:styled-content>\u03b5<\/jats:italic>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Accordingly, PKC<\/jats:styled-content>\u03b5 <\/jats:italic>ASO<\/jats:styled-content>\u2010 and saline\u2010treated mice were fed high\u2010fat control or ethanol (EtOH)\u2010containing enteral diets for 4\u00a0weeks.<\/jats:p><\/jats:sec>Results<\/jats:title>Chronic EtOH exposure significantly elevated hepatic lipid pools as well as activated PKC<\/jats:styled-content>\u03b5<\/jats:italic>. The PKC<\/jats:styled-content>\u03b5 <\/jats:italic>ASO<\/jats:styled-content> partially blunted the increases in hepatic lipids caused by EtOH. Administration of PKC<\/jats:styled-content>\u03b5 <\/jats:italic>ASO<\/jats:styled-content> also completely prevented the increase in the expression of fatty acid synthase, and tumor necrosis factor \u03b1<\/jats:italic> caused by EtOH. Despite these protective effects, the PKC<\/jats:styled-content>\u03b5 <\/jats:italic>ASO<\/jats:styled-content> was unable to prevent the increases in inflammation and necrosis caused by chronic EtOH. These latter results correlated with an inability of the PKC<\/jats:styled-content>\u03b5 <\/jats:italic>ASO<\/jats:styled-content> to blunt the up\u2010regulation of plasminogen activator inhibitor\u20101 (PAI<\/jats:styled-content>\u20101) and the accumulation of fibrin. Importantly, PAI<\/jats:styled-content>\u20101 has been previously shown to more robustly mediate inflammation and necrosis (vs. steatosis) after chronic EtOH exposure.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>This study identifies a novel potential mechanism where EtOH, independent of steatosis, can contribute to liver damage. These results also suggest that PAI<\/jats:styled-content>\u20101 and fibrin accumulation may be at the center of this PKC<\/jats:styled-content>\u03b5<\/jats:italic>\u2010independent pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12324","type":"journal-article","created":{"date-parts":[[2014,1,31]],"date-time":"2014-01-31T17:30:36Z","timestamp":1391189436000},"page":"801-809","source":"Crossref","is-referenced-by-count":1,"title":["PKC<\/scp>\u03b5<\/i> Contributes to Chronic Ethanol\u2010Induced Steatosis in Mice but not Inflammation and Necrosis"],"prefix":"10.1111","volume":"38","author":[{"given":"J. Phillip","family":"Kaiser","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Louisville Health Sciences Center Louisville Kentucky"},{"name":"University of Louisville Alcohol Research Center Louisville Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luping","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Louisville Health Sciences Center Louisville Kentucky"},{"name":"University of Louisville Alcohol Research Center Louisville Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliane I.","family":"Beier","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Louisville Health Sciences Center Louisville Kentucky"},{"name":"University of Louisville Alcohol Research Center Louisville 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