title: Uncoupling protein-2 induction in rat hepatocytes after acute carbon tetrachloride liver injury.
abstract: This study is focused on the role of UCP-2 in hepatic oxidative metabolism following acute CCl(4) administration to rats. UCP-2 mRNA, almost undetectable in the liver of controls, was significantly increased 24 h after CCl(4) administration, peaked at 72 h and then tended to disappear. UCP-2 protein, undetectable in controls, increased 48-72 h after CCl(4) treatment. Experiments with isolated liver cells indicated that in control rats UCP-2 was expressed in non-parenchymal cells and not in hepatocytes, whereas in CCl(4)-treated rats UCP-2 expression was induced in hepatocytes and was not affected in non-parenchymal cells. Addition of CCl(4) to the culture medium of hepatocytes from control rats failed to induce UCP-2 expression. Liver mitochondria from CCl(4)-treated rats showed an increase of H(2)O(2) release at 12-24 h, followed by a rise of TBARS. Vitamin E protected liver from CCl(4) injury and reduced the expression of UCP-2. Treatment with GdCl(3) prior to CCl(4), in order to inhibit Kupffer cells, reduced TBARS and UCP-2 mRNA increase in hepatic mitochondria. Our data indicate that CCl(4) induces the expression of UCP-2 in hepatocytes with a redox-dependent mechanism involving Kupffer cells. A role of UCP-2 in moderating CCl(4)-induced oxidative stress during tissue regeneration after injury is suggested.
authors.affiliation: Dipartimento di Biologia, Università di Genova, Genova, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Demori
authors.forename: Bruno
authors.initials: B
authors.lastname: Burlando
authors.forename: Ezio
authors.initials: E
authors.lastname: Gerdoni
authors.forename: Antonia
authors.initials: A
authors.lastname: Lanni
authors.forename: Emilia
authors.initials: E
authors.lastname: Fugassa
authors.forename: Adriana
authors.initials: A
authors.lastname: Voci
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008115:Liver Regeneration; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000071246:Uncoupling Protein 2; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007473:Ion Channels; D024101:Mitochondrial Proteins; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D014810:Vitamin E; D012313:RNA; D006861:Hydrogen Peroxide; D002251:Carbon Tetrachloride