title: Liver damage and caspase-dependent apoptosis is related to protein malnutrition in mice: effect of methionine.
abstract: This study aimed to determine whether the effects on the mouse liver caused by three periods of feeding a protein-free diet for 5 days followed by a normal complete diet for 5 days (3PFD-CD) are prevented by a constant methionine supply (3PFD+Met-CD). The expressions of carbonic anhydrase III (CAIII), fatty acid synthase (FAS), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glutathione S-transferase P1 (GSTP1) were assessed by proteomics and reverse transcriptase-polymerase chain reactions. The liver redox status was examined by measuring the activities of superoxide dismutase (SOD) and catalase (CAT), as well as protein carbonylation. Because oxidative stress can result in apoptosis, the activity and content of caspase-3, as well as the x-linked inhibitor of the apoptosis protein (XIAP) and mitochondrial caspase-independent apoptosis inducing factor (AIF) contents were assessed. In addition, the liver histomorphology was examined. Compared to the controls fed a normal complete diet throughout, feeding with 3PFD-CD increased the FAS content, decreased the CAIII content, decreased both the SOD and CAT activities, and increased protein carbonylation. It also activated caspase-3, decreased the XIAP content, decreased the AIF content, increased the number of GSTP1-positive foci and caspase-3-positive cells, and caused fatty livers. Conversely, the changes were lessened to varying degrees in mice fed 3PFD+Met-CD. The present results indicate that a regular Met supply lessens the biochemical changes, damage, and caspase-dependent apoptosis provoked by recurrent dietary amino acid deprivation in the mouse liver.
authors.affiliation: Biological Research Institute, Faculty of Natural Sciences, National University of Mar del Plata - CONICET, CC 1245, CP 7600 Mar del Plata, Argentina.
authors.forename: Verónica J
authors.initials: VJ
authors.lastname: Caballero
authors.affiliation: Biological Research Institute, Faculty of Natural Sciences, National University of Mar del Plata - CONICET, CC 1245, CP 7600 Mar del Plata, Argentina.
authors.forename: Julieta R
authors.initials: JR
authors.lastname: Mendieta
authors.affiliation: Institute of Research and Technology in Animal Reproduction (INITRA), Faculty of Veterinary Science. University of Buenos Aires, Av. Chorroarín 280, C1427CWO Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lombardo
authors.affiliation: Institute of Molecular and Cellular Biology, University Miguel Hernandez, Building Torregaitán, Avda de la Universidad s/n, 03202, Elche, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Saceda
authors.affiliation: Institute of Molecular and Cellular Biology, University Miguel Hernandez, Building Torregaitán, Avda de la Universidad s/n, 03202, Elche, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Ferragut
authors.affiliation: Biological Research Institute, Faculty of Natural Sciences, National University of Mar del Plata - CONICET, CC 1245, CP 7600 Mar del Plata, Argentina.
authors.forename: Rubén D
authors.initials: RD
authors.lastname: Conde
authors.affiliation: Biological Research Institute, Faculty of Natural Sciences, National University of Mar del Plata - CONICET, CC 1245, CP 7600 Mar del Plata, Argentina. Electronic address: marcela@umh.es.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Giudici
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D008715:Methionine / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011488:Protein Deficiency / Q000201:enzymology* / Q000473:pathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; C494830:AIFM1 protein, mouse; D051636:X-Linked Inhibitor of Apoptosis Protein; D008715:Methionine; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D051549:Glutathione S-Transferase pi; C496557:Gstp1 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Apoptosis; Liver; Methionine; Mice; Protein depletion