Iron proteins of duodenal enterocytes isolated from mice with genetically and experimentally altered iron metabolism.
The molecular basis for the control of iron absorption by the duodenum remains unknown: however, ferritin (Ft) and the iron status of enterocytes have been suggested as regulatory factors. We determined the iron and Ft status of duodenal enterocytes from mice with hypotransferrinaemia, a genetic defect leading to greatly enhanced iron absorption, and for comparison we also investigated mice with experimentally-altered iron absorption. Duodenal enterocytes were isolated and analysed for Ft and non-haem iron content and for transferrin binding (as a measure of transferrin receptor activity). RNA was extracted from the duodenal mucosa and examined for transferrin receptor and H- and L-Ft mRNA levels by Northern hybridization analysis. Ft levels were elevated in enterocytes of hypotransferrinaemic mice, similar to that seen in iron dextran-injected mice of the CD1-strain. Enterocyte Ft levels were reduced in mice fed a diet diminished in iron, but unchanged in hypoxic mice enterocytes. Enterocytes of hypotransferrinaemic mice had normal non-haem iron levels and transferrin binding; however, enterocytes from CD-1 mice fed a low iron diet had increased transferrin binding and a decreased non-haem iron content. Duodenal mRNA levels for transferrin receptor and H-Ft were unchanged in hypotransferrinaemic mice, whereas L-Ft was increased. We conclude from the Ft and non-haem iron contents and transferrin binding that duodenal enterocytes from hypotransferrinaemic mice are not simply iron deficient, leading to increased expression of iron carriers proteins. Duodenal iron absorption can be enhanced in mice even when enterocyte Ft levels are raised or unchanged, suggesting that iron absorption is regulated by developmentally programmed expression of iron transporters by enterocytes.
Pountney
D J
DJ
Department of Clinical Biochemistry, Guy's King's and St Thomas's School of Medicine, King's College Denmark Hill Campus, London.
Konijn
A M
AM
McKie
A T
AT
Peters
T J
TJ
Raja
K B
KB
Salisbury
J R
JR
Simpson
R J
RJ
D000818:Animals; D004386:Duodenum / Q000166:cytology / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D007408:Intestinal Absorption / Q000235:genetics*; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000235:genetics; D019190:Iron Overload / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014168:Transferrin / Q000378:metabolism
D006454:Hemoglobins; D014168:Transferrin; D006418:Heme; D007501:Iron