title: Proteomic analysis reveals changes in the liver protein pattern of rats exposed to dietary folate deficiency.
abstract: Epidemiologic and experimental studies showed that folate deficiency is associated with increased risk of degenerative diseases by enhancing abnormal one-carbon metabolism. We studied the changes in the proteome of liver, the main tissue of folate storage and metabolism, in a rat model of dietary folate depletion. Four-month-old rats were fed for 4 wk an amino acid-defined diet without folate and compared with pair-fed rats given the same diet adequately supplemented with folic acid. Folate deprivation decreased plasma and hepatic folate concentrations dramatically, while increasing homocysteinemia significantly. Using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight MS, we identified 9 spots corresponding to differentially expressed proteins in the liver of folate-deficient rats compared with controls. Among those spots, 4 had a significantly increased volume, whereas the volume of the 5 other spots was decreased. Upregulated proteins included glutathione peroxidase (GPx) 1 and peroxiredoxin 6, 2 enzymes involved in the response to oxidative stress, and MAWD binding protein (MAWDBP), which has been associated with cancer. MAWDBP was simultaneously identified as a second spot with a lower isoelectric point (pI) that vanished almost completely after folate deficiency. Decreased abundance was also observed for cofilin 1, a protein linked to tumorigenesis, and for the GRP 75 precursor and preproalbumin, both of which are responsive to oxidative stress and/or inflammation. Moreover, an enzyme activity assay and/or Western blot analysis of GPx-1 and MAWDBP confirmed the proteomic findings. Our results show that folate deficiency modifies the abundance of several liver proteins consistently with adaptive tissue responses to oxidative and degenerative processes.
authors.affiliation: Unité Maladies Métaboliques et Micronutriments, Institut National de la Recherche Agronomique, 63122-Saint-Genès Champanelle, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chanson
authors.forename: Thierry
authors.initials: T
authors.lastname: Sayd
authors.forename: Edmond
authors.initials: E
authors.lastname: Rock
authors.forename: Christophe
authors.initials: C
authors.lastname: Chambon
authors.forename: Véronique
authors.initials: V
authors.lastname: Santé-Lhoutellier
authors.forename: Geneviève
authors.initials: G
authors.lastname: Potier de Courcy
authors.forename: Patrick
authors.initials: P
authors.lastname: Brachet
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D015153:Blotting, Western; D004032:Diet; D019587:Dietary Supplements; D015180:Electrophoresis, Gel, Two-Dimensional; D005492:Folic Acid / Q000008:administration & dosage*; D005494:Folic Acid Deficiency / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000032:analysis; D008099:Liver / Q000737:chemistry* / Q000201:enzymology; D008297:Male; D011506:Proteins / Q000032:analysis*; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000596:Amino Acids; D011506:Proteins; D005492:Folic Acid; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat