Proteomic Analysis Reveals Changes in the Liver Protein Pattern of Rats Exposed to Dietary Folate Deficiency

• Published in: The Journal of nutrition Vol. 135; no. 11; pp. 2524 - 2529
• Main Authors: Chanson, Aurélie, Sayd, Thierry, Rock, Edmond, Chambon, Christophe, Santé-Lhoutellier, Véronique, Potier de Courcy, Geneviève, Brachet, Patrick
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutritional Sciences 01.11.2005; American Society for Nutrition
• Subjects: Amino Acids - administration & dosage; animal models; Animals; binding proteins; Biological and medical sciences; blood chemistry; Blotting, Western; Diet; Dietary Supplements; Electrophoresis, Gel, Two-Dimensional; enzyme activity; Feeding. Feeding behavior; folic acid; Folic Acid - administration & dosage; Folic Acid Deficiency - metabolism; Food and Nutrition; Fundamental and applied biological sciences. Psychology; gene expression; glutathione peroxidase; Glutathione Peroxidase - analysis; Glutathione Peroxidase GPX1; homocysteine; isoelectric point; Life Sciences; Liver - chemistry; Liver - enzymology; liver protein; Male; nutrient deficiencies; nutrient intake; nutritional status; oxidative stress; peroxidases; peroxiredoxin; protein synthesis; Proteins - analysis; Proteomics; Rats; Rats, Wistar; Sensitivity and Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Vertebrates: anatomy and physiology, studies on body, several organs or systems; homocysteine; folate deprivation; Nutrition; Rat; proteomics; Digestive system; Enzyme; Deficiency; Liver; Rodentia; antioxidant enzymes; Antioxidant; Folic acid; Folate; Protein; Micronutrient; Vertebrata; Mammalia; Homocystein; Animal; hepatic proteins; PROTEOMIC; HOMOCYSTEINE; RAT; CONTROLE DE MALADIES; ANTIOXIDANT ENZYME; HEPATIC PROTEIN; PROTEINE HEPATIQUE; FOLATE DEPRIVATION; CARENCE EN VITAMINE
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/135.11.2524

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.