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.