Divalent Metal Transporter (divalent + metal_transporter)

Distribution by Scientific Domains


Selected Abstracts


The Effects of Inhibition of Haem Biosynthesis by Griseofulvin on Intestinal Iron Absorption

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2004
Abas H. Laftah
Urinary 5-aminolaevulinic acid levels were increased within 24 hr of feeding mice with griseofulvin diet (2.5% w/w), with more marked increases seen after 3,7 days. Urinary porphobilinogen levels also showed a similar trend. In vivo intestinal iron absorption was significantly reduced (P<0.05) in experimental mice, mainly due to reduction in the transfer of 59Fe from the enterocytes to the portal circulation. In vitro studies using isolated duodenal fragments also exhibited marked decreases in both iron uptake and Fe (III) reduction. Changes in mucosal Divalent Metal Transporter 1 (DMT-1), Dcytb and Ireg1 (iron regulated protein 1) mRNA levels paralleled the changes in iron absorption. The reduction in iron absorption after griseofulvin treatment was normalised when mice were simultaneously injected with haem-arginate. These data support the hypothesis that intermediates in haem biosynthesis, particularly 5-aminolaevulinic acid, regulate intestinal iron absorption. [source]


Divalent metal transporter 1 up-regulation is involved in the 6-hydroxydopamine-induced ferrous iron influx

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2007
Ning Song
Abstract The reasons underlying the high iron content found in the substantia nigra (SN) of Parkinson's disease (PD) are largely unknown. We suppose, based on our previous studies, that the newly discovered iron transporter divalent metal transporter 1 (DMT1) might be involved in this SN iron accumulation process. To investigate this, we first observed the cellular expression of DMT1 in rat SN, both with the iron response element (+IRE) and without the IRE (,IRE) forms. The results showed that both forms of DMT1 were expressed on neurons, astrocytes, and microglia but not on oligodendrocytes. We further observed the relationship between the increased iron influx and DMT1 expression in 6-hydroxydopamine (6-OHDA)-treated C6 cells. 6-OHDA (10 ,mol/liter) caused a significant increase in ferrous iron influx, with the increased expression of DMT1+IRE, both in protein and in mRNA levels, whereas no change was observed for DMT1,IRE. To clarify further that the increased expression of DMT1 was not due to the increased intracellular iron content, C6 cells were overloaded with ferric ammonium citrate (100 ,g/ml). Decreased expression of both forms of DMT1 was observed. Our data suggest that DMT1 is highly expressed in rat SN in a cell-specific manner. Increased DMT1+IRE expression is the mechanism behind ferrous iron influx induced by 6-OHDA treatment in C6 cells. This may give some evidence for the involvement of DMT1 in the iron accumulation in PD. © 2007 Wiley-Liss, Inc. [source]


The role of ZIP8 down-regulation in cadmium-resistant metallothionein-null cells

JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2009
Hitomi Fujishiro
Abstract The mechanisms of cellular cadmium uptake in mammalian cells remain obscure. To solve this problem, we established cadmium-resistant cells (A7 and B5) from metallothionein-null mouse cells, and found that cadmium accumulation was markedly suppressed in these cells. DNA microarray and real-time PCR analyses revealed that expressions of ZIP (Zrt-, Irt-related protein) 8 and ZIP14 were down-regulated in A7 and B5 cells. In particular, both mRNA and protein levels of ZIP8 were markedly suppressed in A7 and B5 cells. Introduction of short hairpin RNA (shRNA) of ZIP8 into parental cells reduced the accumulation of cadmium to about 35% of that of mock-transfected cells, whereas the introduction of shRNA of divalent metal transporter 1 hardly changed cadmium accumulation. Thus, the cadmium resistance in A7 and B5 cells may be conferred primarily by the down-regulation of ZIP8. In mouse tissues, high expression of ZIP8 was noted in the liver, kidney, lung and testis. These data suggest that ZIP8 plays an important role in cellular uptake of cadmium. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Divalent metal transporter 1 up-regulation is involved in the 6-hydroxydopamine-induced ferrous iron influx

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2007
Ning Song
Abstract The reasons underlying the high iron content found in the substantia nigra (SN) of Parkinson's disease (PD) are largely unknown. We suppose, based on our previous studies, that the newly discovered iron transporter divalent metal transporter 1 (DMT1) might be involved in this SN iron accumulation process. To investigate this, we first observed the cellular expression of DMT1 in rat SN, both with the iron response element (+IRE) and without the IRE (,IRE) forms. The results showed that both forms of DMT1 were expressed on neurons, astrocytes, and microglia but not on oligodendrocytes. We further observed the relationship between the increased iron influx and DMT1 expression in 6-hydroxydopamine (6-OHDA)-treated C6 cells. 6-OHDA (10 ,mol/liter) caused a significant increase in ferrous iron influx, with the increased expression of DMT1+IRE, both in protein and in mRNA levels, whereas no change was observed for DMT1,IRE. To clarify further that the increased expression of DMT1 was not due to the increased intracellular iron content, C6 cells were overloaded with ferric ammonium citrate (100 ,g/ml). Decreased expression of both forms of DMT1 was observed. Our data suggest that DMT1 is highly expressed in rat SN in a cell-specific manner. Increased DMT1+IRE expression is the mechanism behind ferrous iron influx induced by 6-OHDA treatment in C6 cells. This may give some evidence for the involvement of DMT1 in the iron accumulation in PD. © 2007 Wiley-Liss, Inc. [source]


Regulatory mechanisms of intestinal iron absorption,Uncovering of a fast-response mechanism based on DMT1 and ferroportin endocytosis

BIOFACTORS, Issue 2 2010
Marco T. Núñez
Abstract Knowledge on the intestinal iron transport process and the regulation of body iron stores has greatly increased during the last decade. The liver, through the sensing of circulating iron, is now recognized as the central organ in this regulation. High iron levels induce the synthesis of hepcidin, which in turn decreases circulating iron by inhibiting its recycling from macrophages and its absorption at the intestine. Another mechanism for the control of iron absorption by the enterocyte is an active Iron Responsive Element (IRE)/Iron Regulatory Protein (IRP) system. The IRE/IRP system regulates the expression of iron uptake and storage proteins thus regulating iron absorption. Similarly, increasing evidence points to the transcriptional regulation of both divalent metal transporter 1 (DMT1) and ferroportin expression. A new mechanism of regulation related to a phenomenon called the mucosal block is starting to be unveiled. The mucosal block describes the ability of an initial dose of ingested iron to block absorption of a second dose given 2,4 h later. Here, we review the mechanisms involved in the expression of DMT1 and ferroportin, and present recent evidence on the molecular components and cellular processes involved in the mucosal block response. Our studies indicate that mucosal block is a fast-response endocytic mechanism destined to decrease intestinal iron absorption during a high ingest of iron. [source]