Vitamin C Differentially Impacts the Serum Proteome Profile in Female and Male Mice

A suboptimal blood vitamin C (ascorbate)
level increases the risk
of several chronic diseases. However, the detection of hypovitaminosis
C is not a simple task, as ascorbate is unstable in blood samples.
In this study, we examined the serum proteome of mice lacking the
gulonolactone oxidase (Gulo) required for the ascorbate biosynthesis. Gulo–/– mice were
supplemented with different concentrations of ascorbate in drinking
water, and serum was collected to identify proteins correlating with
serum ascorbate levels using an unbiased label-free liquid chromatography-tandem
mass spectrometry global quantitative proteomic approach. Parallel
reaction monitoring was performed to validate the correlations. We
uncovered that the serum proteome profiles differ significantly between
male and female mice. Also, unlike Gulo–/– males, a four-week ascorbate treatment
did not entirely re-establish the serum proteome profile of ascorbate-deficient Gulo–/– females
to the optimal profile exhibited by Gulo–/– females that never experienced an
ascorbate deficiency. Finally, the serum proteins involved in retinoid
metabolism, cholesterol, and lipid transport were similarly affected
by ascorbate levels in males and females. In contrast, the proteins
regulating serum peptidases and the protein of the acute phase response
were different between males and females. These proteins are potential
biomarkers correlating with blood ascorbate levels and require further
study in standard clinical settings. The complete proteomics data
set generated in this study has been deposited to the public repository
ProteomeXchange with the data set identifier: PXD027019.