Inhibition by IFNa-2b of rat liver.regeneration: Effect on ODC protein expression and total protein synthesis

CRISTIÁN FAVRE; CRISTINA E. CARNOVALE; JUAN A. MONTI; MARÍA CRISTINA CARRILLO

BIOCHEMICAL PHARMACOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2001 vol. 61 p. 1587 - 1593

0006-2952

Polyamines are key factors in macromolecule synthesis during liver regeneration. It has been postulated that interferon-alpha (IFNalpha) decreases putrescine levels in regenerating liver by inhibiting ornithine decarboxylase (ODC) activity, the main enzyme in polyamine biosynthesis. In the present study, we analysed the effects of a pharmacological dose of IFNalpha on polyamine and ODC levels during the regenerative process following partial hepatectomy in rats. Synthesis of ODC by isolated hepatocytes from IFN-treated rats with regenerating livers was also assessed. Furthermore, we investigated the effect of IFNalpha-2b on DNA and total protein synthesis in 24-hr regenerating livers. No effect on DNA synthesis was observed at the dose of IFNalpha-2b used, but total protein synthesis decreased significantly in IFNalpha-2b-treated rats undergoing liver regeneration (7.0 +/- 2.0 and 12.1 +/- 1.7%. min(-1) in hepatectomized rats treated with IFNalpha-2b and saline, respectively). ODC levels were also reduced significantly (by 50%) in hepatectomized rats treated with IFNalpha-2b versus saline. In parallel with the ODC decrease, the concentrations of putrescine and spermidine (63 +/- 25 vs 101 +/- 15 nmol/g liver and 1.08 +/- 0.35 vs 2.14 +/- 0.22 micromol/g liver, respectively, in IFNalpha-2b- and saline-treated hepatectomized rats) showed similar, significant diminutions. Moreover, the incorporation of [35S]methionine into ODC was decreased dramatically in isolated hepatocytes from IFNalpha-2b-treated hepatectomized rats 12 hr after surgery. In conclusion, the protein synthesis rate in regenerating liver was impaired by therapeutic doses of IFNalpha-2b. In addition, the results presented in this study suggest that IFNalpha-2b negatively regulates ODC synthesis, causing a reduction in polyamine levels during liver regeneration.