title: Role of PPARα in the attenuation of bile acid-induced apoptosis by omega-3 long-chain polyunsaturated fatty acids in cultured hepatocytes.
abstract: Omega-3 long-chain polyunsaturated fatty acids (ω3PUFA) have been shown to be antiinflammatory in the attenuation of hepatocellular injury. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor transcription factor that inhibits the activation of nuclear factor κB, thereby repressing inflammation, and ωPUFA are PPARα ligands. The purpose of this study was to determine if ω3PUFA attenuate bile acid-induced apoptosis via PPARα.
  
  
  
  Human hepatocellular carcinoma (HepG2) cells were treated with chenodeoxycholic acid (CDCA) ± ω3PUFA. Activation of PPARα was evaluated, and expression of PPARα, farnesoid X receptor, liver X receptor alpha (LXRα), and retinoid X receptor mRNA was evaluated by reverse-transcriptase PCR.
  
  
  
  PPARα activation was increased in HepG2 cells treated with ω3PUFA, and decreased in the presence of CDCA when compared with untreated cells. PPARα mRNA was reduced by 67% with CDCA and restored to the level of control with ω3PUFA. LXRα mRNA increased twofold with CDCA treatment and was significantly reduced by ω3PUFA.
  
  
  
  Expression of PPARα, as well as LXRα mRNA levels, was reduced with CDCA treatment and restored with the addition of ω3PUFA. These results suggest that PPARα and LXRα may be mediators by which ω3PUFA attenuate bile acid-induced hepatocellular injury.
authors.affiliation: Department of Clinical Pharmacy, The University of Tennessee Health Science Center, Memphis, Tennessee.|Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee.|Le Bonheur Children's Hospital, Memphis, Tennessee.|Children's Foundation Research Institute, Memphis, Tennessee.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Tillman
authors.affiliation: Department of Clinical Pharmacy, The University of Tennessee Health Science Center, Memphis, Tennessee.|Children's Foundation Research Institute, Memphis, Tennessee.
authors.forename: Peihong
authors.initials: P
authors.lastname: Guan
authors.affiliation: Department of Clinical Pharmacy, The University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Howze
authors.affiliation: Department of Clinical Pharmacy, The University of Tennessee Health Science Center, Memphis, Tennessee.|Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Helms
authors.affiliation: Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee.|Le Bonheur Children's Hospital, Memphis, Tennessee.|Children's Foundation Research Institute, Memphis, Tennessee.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Black
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry; D017209:Apoptosis; D001647:Bile Acids and Salts / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008024:Ligands; D008099:Liver / Q000276:immunology; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001647:Bile Acids and Salts; D015525:Fatty Acids, Omega-3; D008024:Ligands; D047493:PPAR alpha; D047495:PPAR gamma; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7