Inactivation of Sirt1 in mouse livers protects against endotoxemic liver injury by acetylating and activating NF-κB.

ABSTRACT: Sirtuin 1 (Sirt1) is a deacetylase that regulates many cellular processes in the liver, and so far its role in endotoxemic liver injury is elusive. So we conditionally inactivate Sirt1 in murine hepatocytes to determine its role in d-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-κB response because knockdown of RelA/p65 negates the protective effect of Sirt1 knockout. Mechanistically, NF-κB p65 is maintained in a hyperacetylated, DNA-binding competent state in tumor necrosis factor-α (TNF-α)-challenged albumin-Cre⁺ (AlbCre⁺) hepat

SUBMITTER: Cui X 

PROVIDER: S-EPMC5133964 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature