Proteome-Driven Elucidation of Adaptive Responses to Combined Vitamin E and C Deficiency in Zebrafish

The purpose of this study was to determine the system-wide consequences
of deficiencies in two essential micronutrients, vitamins E and C,
on the proteome using zebrafish (Danio rerio) as
one of the few vertebrate models that similar to humans cannot synthesize
vitamin C. We describe a label-free proteomics workflow to detect
changes in protein abundance estimates dependent on vitamin regimes.
We used ion-mobility-enhanced data-independent tandem mass spectrometry
to determine differential regulation of proteins in response to low
dietary levels of vitamin C with or without vitamin E. The detection
limit of the method was as low as 20 amol, and the dynamic range was
five orders of magnitude for the protein-level estimates. On the basis
of the quantitative changes obtained, we built a network of protein
interactions that reflect the whole organism’s response to
vitamin C deficiency. The proteomics-driven study revealed that in
vitamin-E-deficient fish, vitamin C deficiency is associated with
induction of stress response, astrogliosis, and a shift from glycolysis
to glutaminolysis as an alternative mechanism to satisfy cellular
energy requirements.