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So we conditionally inactivate Sirt1 in murine hepatocytes to determine its role in\n                    <jats:sc>d<\/jats:sc>\n                    -galactosamine (GalN)\/lipopolysaccharide (LPS)-induced liver damage, which is a well-established experimental model mimicking septic liver injury and fulminant hepatitis. Ablation of Sirt1 shows remarkable protection against GalN\/LPS-induced liver injury, which is a result of enhanced NF-\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B response because knockdown of RelA\/p65 negates the protective effect of Sirt1 knockout. Mechanistically, NF-\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B p65 is maintained in a hyperacetylated, DNA-binding competent state in tumor necrosis factor-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (TNF-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    )-challenged albumin-Cre\n                    <jats:sup>+<\/jats:sup>\n                    (AlbCre\n                    <jats:sup>+<\/jats:sup>\n                    ) hepatocytes. Transfection of hepatocytes with a recombinant acetylated p65 expression construct replicates the protection afforded by Sirt1 knockout. Transfection of AlbCre\n                    <jats:sup>+<\/jats:sup>\n                    hepatocytes with a recombinant wild-type Sirt1 construct, rather than a deacetylase-defective one, compromises NF-\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B activation and resensitizes hepatocytes to TNF-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -induced apoptosis. Taken together, our results demonstrate that Sirt1 deacetylates p65 and compromises NF-\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B activity in hepatocytes when confronted with LPS\/TNF-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    stimulation, leading to increased susceptibility to endotoxemic injury. These findings identify a possible protein effector to maneuver the hepatic NF-\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B signaling pathway under inflammatory circumstances and a feasible way to increase hepatocellular resistance to endotoxin\/TNF-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    toxicity.\n                  <\/jats:p>","DOI":"10.1038\/cddis.2016.270","type":"journal-article","created":{"date-parts":[[2016,10,6]],"date-time":"2016-10-06T08:48:14Z","timestamp":1475743694000},"page":"e2403-e2403","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Inactivation of Sirt1 in mouse livers protects against endotoxemic liver injury by acetylating and activating NF-\u03baB"],"prefix":"10.1038","volume":"7","author":[{"given":"Xiaolan","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longmei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,6]]},"reference":[{"key":"BFcddis2016270_CR1","first-page":"1730","volume":"61","author":"Q Wan","year":"2014","unstructured":"Wan Q, Ye Q, Su T, Zhou J . 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