Inactivation of hepatocyte nuclear factor-4{alpha} mediates alcohol-induced downregulation of intestinal tight junction proteins.

ABSTRACT: Chronic alcohol exposure has been shown to increase the gut permeability in the distal intestine, in part, through induction of zinc deficiency. The present study evaluated the molecular mechanisms whereby zinc deficiency mediates alcohol-induced intestinal barrier dysfunction. Examination of zinc finger transcription factors in the gastrointestinal tract of mice revealed a prominent distribution of hepatocyte nuclear factor-4alpha (HNF-4alpha). HNF-4alpha exclusively localizes in the epithelial nuclei and exhibited an increased abundance in mRNA and protein levels in the distal intestine. Chronic alcohol exposure to mice repressed the HNF-4alpha gene expression in the ileum and reduced the protein level and DNA binding activity of HNF-4alpha in all of the intestinal segments with the most

SUBMITTER: Zhong W 

PROVIDER: S-EPMC2950677 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature