An Iron-Regulated Ferric Reductase Associated with the Absorption of Dietary Iron

Abstract

The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane of duodenal enterocytes, and induced ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of Dcytb messenger RNA and protein were regulated by changes in physiological modulators of iron absorption. Thus, Dcytb provides an important element in the iron absorption pathway.

Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis

“…All 16 subjects with positive hepatic iron staining had underlying hepatocellular causes of cirrhosis and 15 (94%) were men. Subjects with positive iron staining had higher Child-Pugh scores (10 [5-13] vs. 6 [5][6][7][8][9][10][11][12][13][14], respectively, P ϭ .003) compared with subjects with negative iron staining. Seven (44%) patients had acanthocytes.…”

“…Within the cirrhosis group, subjects with hepatocellular cirrhosis had more severe liver disease than subjects with cholestasis-induced cirrhosis. This finding was reflected in a higher Child-Pugh score (9 [5][6][7][8][9][10][11][12][13][14] vs. 5 [5][6][7][8][9], P ϭ .004), a higher MELD score (15.3 Ϯ 6.3 vs. 10.0 Ϯ 3.9, P ϭ .02), increased prothrombin time (15.3 Ϯ 4.2 vs. 11.6 Ϯ 2.2, P ϭ .006), and a lower serum albumin level (28.7 Ϯ 6.4 vs. 35.5 Ϯ 5.0, P ϭ .003).…”

“…A ferrireductase, duodenal cytochrome b (Dcytb), was identified recently on the brush border membrane of duodenal enterocytes in mice. 14 A putative duodenal basolateral iron transporter gene was identified independently by several groups and termed iron regulated gene 1 (Ireg1), ferroportin1, or metal transporter protein 1 (MTP1). [15][16][17] Ireg1 functions as an iron exporter and likely requires the presence of auxiliary ferroxidase activity.…”

Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5)

“…Antiserum against duodenal cytochrome b (DCytb) was previously described and kindly provided by Dr. Andrew McKie (King's College, London, UK) (McKie et al, 2001). Cell culture supernatant containing rat monoclonal antibody against the epithelial marker 4.8H1 was previously described (De Lisle and Ziemer, 2000) and kindly provided by Dr. Robert DeLisle (University of Kansas Medical Center, Kansas City, KS, USA).…”

Effects of Intracerebroventricular Injection of Iron Dextran on the Iron Concentration and Divalent Metal Transporter 1 Expression in the Caudate Putamen and Substantia Nigra of Rats

“…Divalent metal transporter 1 (DMT1) is the first identified mammalian transmembrane iron transporter, and it is also known as natural resistance associated macrophage protein 2/divalent cation transporter/solute carrier family 11, member a2 (Nramp2/DCT1/Slc11a2) (Gruenheid et al, 1995;Andrews, 1999;Touret et al, 2003). DMT1 has been shown to transport a variety of divalent metals including Fe 21 Harris et al, 1999;McKie et al, 2001). There are at least two different splice forms of DMT1: DMT1 (1IRE) mRNA containing iron-responsive element (IRE) in the 3 0 -UTR and DMT1 (2IRE) mRNA not containing a classical IRE (Gunshin et al, 1997;Lee et al, 1998).…”