title: Proteomic analysis shows the upregulation of erythrocyte dematin in zinc-restricted human subjects.
abstract: BACKGROUND
  Although the importance of adequate zinc intake has been known for decades, the estimated global prevalence of zinc deficiency remains high. This substantiates the need for a specific and sensitive status assessment tool.
  
  
  OBJECTIVE
  The objective was to evaluate erythrocyte zinc transporters as candidate molecules with the potential of being a biomarker of dietary zinc status in humans.
  
  
  METHODS
  A 24-d observational study with acclimation (7 d, 10.4 mg Zn/d), zinc-depletion (10 d, 0.3 mg Zn/d), and zinc-repletion (7 d, 29.5 mg Zn/d) phases was conducted in healthy men (n = 9). Proteomic approaches including Western blot analyses and tandem mass spectrometry were implemented to identify the zinc responsiveness of selected red blood cell membrane proteins.
  
  
  RESULTS
  Zinc transporter 1 (ZnT1) and Zrt/Irt-like proteins ZIP8 and ZIP10 were detected in human erythrocyte membranes. No effects of short-term dietary zinc depletion were observed on the amounts of these proteins. However, changes in a cytoskeletal protein, dematin, by zinc depletion were identified through the nonspecific signals produced by an anti-ZIP8 antibody. This response was further validated by a dematin-specific antibody and with erythrocytes collected from mice fed a zinc-deficient diet.
  
  
  CONCLUSIONS
  The presence of ZnT1, ZIP8, and ZIP10 in human red blood cells implicates their role in the regulation of cellular zinc metabolism in the human erythroid system. The zinc responsiveness of membrane dematin suggests its capability to serve as a biomarker for dietary zinc depletion and its involvement in impaired erythroid membrane fragility by zinc restriction. This trial was registered at clinicaltrials.gov as NCT01221129.
authors.affiliation: Food Science and Human Nutrition Department, Center for Nutritional Sciences, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL, USA.
authors.forename: Moon-Suhn
authors.initials: MS
authors.lastname: Ryu
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Guthrie
authors.forename: Alyssa B
authors.initials: AB
authors.lastname: Maki
authors.forename: Tolunay B
authors.initials: TB
authors.lastname: Aydemir
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cousins
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009752:Nutritional Status; D020543:Proteome / Q000032:analysis*; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation; D055815:Young Adult; D015032:Zinc / Q000008:administration & dosage* / Q000172:deficiency*
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D027682:Cation Transport Proteins; C044805:DMTN protein, human; D008840:Microfilament Proteins; D020543:Proteome; C498299:SLC30A1 protein, human; C519886:SLC39A10 protein, human; C530151:SLC39A8 protein, human; C017800:zinc-binding protein; D015032:Zinc