Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco-2 cells.
Iron deficiency is the most common nutritional disorder worldwide, whereas pathologic elevations of body iron stores can occur under certain circumstances due to genetic abnormalities or in association with other diseases. The intestine is the exclusive locus of homeostatic regulation of body iron stores, which is accomplished by changes in iron absorption efficiency by largely unknown molecular mechanisms in response to alterations in body iron stores. Recently, a number of novel genes involved in iron metabolism, such as the iron uptake transporter DMT1/DCT1/Nramp2 and the iron export transporter IREG1/ferroportin1/MTP1, have been identified, providing important insights about molecular aspects of intestinal iron absorption and its regulation. The aim of this study was to investigate the effects of iron treatment on DMT1 and IREG1 mRNA expression in Caco-2 cells, a human intestinal cell line. Exposure of the cells to iron (200 micromol/L ferric nitrilotriacetic acid for 72 h) significantly decreased transferrin receptor mRNA (80%), DMT1 mRNA (57%) and IREG1 mRNA (52%). These observations are consistent with the notion of parallel regulation of these iron-responsive genes in vivo to protect the enterocyte from iron toxicity and mediate a decreased efficiency of intestinal iron absorption to prevent iron overload.
Martini
Ligia A
LA
Mineral Bioavailability Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Tchack
Laurie
L
Wood
Richard J
RJ
D018938:Caco-2 Cells / Q000187:drug effects*; D027682:Cation Transport Proteins / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000627:therapeutic use*; D000090463:Iron Deficiencies; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000187:drug effects / Q000235:genetics*; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D007501:Iron; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000099236:Solute Carrier Family 11, Member 2