Proteome-driven elucidation of adaptive responses to combined vitamin E and C deficiency in zebrafish

J Proteome Res. 2014 Mar 7;13(3):1647-56. doi: 10.1021/pr401108d. Epub 2014 Feb 10.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / metabolism*
  • Ascorbic Acid Deficiency / metabolism*
  • Chromatography, Liquid
  • Humans
  • Mass Spectrometry / methods
  • Metabolic Networks and Pathways
  • Protein Interaction Mapping
  • Proteome / analysis*
  • Proteome / metabolism
  • Tissue Extracts / chemistry
  • Vitamin E / administration & dosage
  • Vitamin E / metabolism*
  • Vitamin E Deficiency / metabolism*
  • Zebrafish


  • Proteome
  • Tissue Extracts
  • Vitamin E
  • Ascorbic Acid