Dietary iron induces rapid changes in rat intestinal divalent metal transporter expression.
The divalent metal transporter (DMT1, also known as NRAMP2 or DCT1) is the likely target for regulation of intestinal iron absorption by iron stores. We investigated changes in intestinal DMT1 expression after a bolus of dietary iron in iron-deficient Belgrade rats homozygous for the DMT1 G185R mutation (b/b) and phenotypically normal heterozygous littermates (+/b). Immunofluorescent staining with anti-DMT1 antisera showed that DMT1 was located in the brush-border membrane. Duodenal DMT1 mRNA and protein levels were six- and twofold higher, respectively, in b/b rats than in +/b rats. At 1.5 h after dietary iron intake in +/b and b/b rats, DMT1 was internalized into cytoplasmic vesicles. At 1.5 and 3 h after iron intake in +/b and b/b rats, there was a rapid decrease of DMT1 mRNA and a transient increase of DMT1 protein. The decrease of DMT1 mRNA was specific, because ferritin mRNA was unchanged. After iron intake, an increase in ferritin protein and decrease in iron-regulatory protein binding activity occurred, reflecting elevated intracellular iron pools. Thus intestinal DMT1 rapidly responds to dietary iron in both +/b and b/b rats. The internalization of DMT1 may be an acute regulatory mechanism to limit iron uptake. In addition, the results suggest that in the Belgrade rat DMT1 with the G185R mutation is not an absolute block to iron.
Yeh
K Y
KY
Section of Hematology/Oncology, Departments of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA. Kyeh@LSUHSC.edu
Yeh
M
M
Watkins
J A
JA
Rodriguez-Paris
J
J
Glass
J
J
D018798:Anemia, Iron-Deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D027682:Cation Transport Proteins; D005260:Female; D005293:Ferritins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006706:Homeostasis / Q000502:physiology; D007202:Indicators and Reagents / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019266:Iron, Dietary / Q000494:pharmacology*; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005293:Ferritins; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D019266:Iron, Dietary; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D008164:Luminescent Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000099236:Solute Carrier Family 11, Member 2