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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.
AuthorsAurélie Chanson, Thierry Sayd, Edmond Rock, Christophe Chambon, Véronique Santé-Lhoutellier, Geneviève Potier de Courcy, Patrick Brachet
JournalThe Journal of nutrition (J Nutr) Vol. 135 Issue 11 Pg. 2524-9 (Nov 2005) ISSN: 0022-3166 [Print] United States
PMID16251605 (Publication Type: Journal Article)
Chemical References
  • Amino Acids
  • Proteins
  • Folic Acid
  • Glutathione Peroxidase
  • Glutathione Peroxidase GPX1
  • Gpx1 protein, rat
Topics
  • Amino Acids (administration & dosage)
  • Animals
  • Blotting, Western
  • Diet
  • Dietary Supplements
  • Electrophoresis, Gel, Two-Dimensional
  • Folic Acid (administration & dosage)
  • Folic Acid Deficiency (metabolism)
  • Glutathione Peroxidase (analysis)
  • Liver (chemistry, enzymology)
  • Male
  • Proteins (analysis)
  • Proteomics
  • Rats
  • Rats, Wistar
  • Sensitivity and Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Glutathione Peroxidase GPX1

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