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.