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Vitamin C alters the amount of specific endoplasmic reticulum associated proteins involved in lipid metabolism in the liver of mice synthesizing a nonfunctional Werner syndrome (Wrn) mutant protein

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  • Lucie Aumailley
  • Florence Roux-Dalvai
  • Isabelle Kelly
  • Arnaud Droit
  • Michel Lebel

Abstract

Werner syndrome (WS) is a premature aging disorder caused by mutations in a protein containing both a DNA exonuclease and DNA helicase domain. Mice lacking the helicase domain of the Wrn protein orthologue exhibit transcriptomic and metabolic alterations, some of which are reversed by vitamin C. Recent studies on these animals indicated that the mutant protein is associated with enriched endoplasmic reticulum (ER) fractions of tissues resulting in an ER stress response. In this study, we identified proteins that exhibit actual level differences in the ER enriched fraction between the liver of wild type and Wrn mutant mice using quantitative proteomic profiling with label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Multiple Reaction Monitoring (MRM) and immunoblotting were performed to validate findings in a secondary independent cohort of wild type and Wrn mutant mice. DAVID 6.7 (NIH) was used for functional annotation analysis and indicated that the identified proteins exhibiting level changes between untreated wild type, Wrn mutant, and vitamin C treated Wrn mutant mice (ANOVA P–value

Suggested Citation

  • Lucie Aumailley & Florence Roux-Dalvai & Isabelle Kelly & Arnaud Droit & Michel Lebel, 2018. "Vitamin C alters the amount of specific endoplasmic reticulum associated proteins involved in lipid metabolism in the liver of mice synthesizing a nonfunctional Werner syndrome (Wrn) mutant protein," PLOS ONE, Public Library of Science, vol. 13(3), pages 1-23, March.
  • Handle: RePEc:plo:pone00:0193170
    DOI: 10.1371/journal.pone.0193170
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    1. Antony Young, 2014. "1 + 1 = 3," Palgrave Macmillan Books, in: Brand Media Strategy, edition 0, chapter 0, pages 81-99, Palgrave Macmillan.
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