Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation.
BACKGROUND
The role of intestinal transporter regulation in optimising nutrient absorption has been studied extensively in rodent and cell line models but not in human subjects.


OBJECTIVE
The aim of the present study was to investigate the response in vivo of zinc transporters in the human enterocyte to dietary zinc supplementation.


METHODS
Eighteen patients who had previously undergone ileostomy, all free of any symptoms of inflammatory bowel disease.


METHODS
Subjects took a daily zinc supplement of 25 mg for 14 days in a double blind, placebo controlled, crossover trial. The effect of the supplement on expression in ileal biopsies of the zinc transporters SLC30A1, SLC30A4, SLC30A5, SLC39A1, SLC39A4, and metallothionein was measured by reverse transcription-polymerase chain reaction RT-PCR. Expression of SLC30A1, SLC30A5, and SLC39A4 was also examined by immunoblotting.


RESULTS
The zinc supplement reduced SLC30A1 mRNA (1.4-fold) together with SLC30A1, SLC30A5, and SLC39A4 protein (1.8-fold, 3.7-fold, and to undetectable levels, respectively) in ileal mucosa and increased metallothionein mRNA (1.7-fold). The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA. Localisation of SLC30A5 at the apical human enterocyte/colonocyte membrane and also at the apical membrane of Caco-2 cells was demonstrated by immunohistochemistry. Commensurate with these observations in zinc supplemented human subjects, SLC30A1, SLC30A5, and SLC39A4 mRNA and protein were reduced in Caco-2 cells cultured at 200 muM compared with 100 muM zinc.


CONCLUSIONS
These observations indicate that, in response to variations in dietary zinc intakes, regulated expression of plasma membrane zinc transporters in the human intestine contributes to maintenance of zinc status.
Cragg
R A
RA
Institute for Cell and Molecular Biosciences, University of Newcastle, The Medical School, Newcastle upon Tyne NE2 4HH, UK.
Phillips
S R
SR
Piper
J M
JM
Varma
J S
JS
Campbell
F C
FC
Mathers
J C
JC
Ford
D
D
D000328:Adult; D000368:Aged; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015032:Zinc / Q000494:pharmacology*
D002352:Carrier Proteins; D012333:RNA, Messenger; C017800:zinc-binding protein; D015032:Zinc