title: Chronic alcohol exposure alters gene expression in HepG2 cells.
abstract: BACKGROUND
  The liver is the primary site of alcohol metabolism and is highly vulnerable to injuries due to chronic alcohol abuse. Several molecular mechanisms, including oxidative stress and altered cellular metabolism, have been implicated in the development and progression of alcoholic liver disease. We sought to gain further insight into the molecular pathogenesis by studying the effects of ethanol exposure on the global gene expression in HepG2 cells.
  
  
  METHODS
  HepG2 cells were cultured in the presence or absence of 75 mM ethanol for 9 days, with fresh media daily. Global gene expression changes were studied using Affymetrix GeneChip(®) Human Exon 1.0 ST Arrays. Gene expression differences were validated for 13 genes by quantitative real-time RT-PCR. To identify biological pathways affected by ethanol treatment, differentially expressed genes were analyzed by Ingenuity Pathway Analysis software.
  
  
  RESULTS
  Long-term ethanol exposure altered the expression of 1,093 genes (false discovery rate ≤ 3%); many of these changes were modest. Long-term ethanol exposure affected several pathways, including acute phase response, amino acid metabolism, carbohydrate metabolism, and lipid metabolism.
  
  
  CONCLUSIONS
  Global measurements of gene expression show that a large number of genes are affected by chronic ethanol, although most show modest effect. These data provide insight into the molecular pathology resulting from extended alcohol exposure.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202-5122, USA.
authors.forename: Sirisha
authors.initials: S
authors.lastname: Pochareddy
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism; D000596:Amino Acids / Q000187:drug effects / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000378:metabolism / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000596:Amino Acids; D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D000431:Ethanol