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Biomedical subjects

G O Latunde-Dada

Publications and source records attributed to G O Latunde-Dada.

17 recordsLinked to original sources
PubMed2004

Tissue-specific changes in iron metabolism genes in mice following phenylhydrazine-induced haemolysis.

Iron metabolism in animals is altered by haemolytic anaemia induced by phenylhydrazine (PHZ). In common with a number of other modulators of iron metabolism, the mode and the mechanisms of this response are yet to be determined. However, recent studies have shown increased expression of the ferrous transporter DMT1 in the duodenum and other tissues of mice administered PHZ. We examined the expression of the ferric reductase Dcytb, DMT1 and some other genes involved in Fe metabolism in tissues of mice dosed with PHZ. The expression of iron-related genes in the duodenum, liver, and spleen of the mice were evaluated using Northern blot analyses, RT-PCR and immunocytochemistry. Dcytb, and DMT1 mRNA and protein increased markedly in the duodenum of mice given PHZ. The efflux protein Ireg1 also increased in the duodenum of the treated mice. These changes correlated with a decrease in hepatic hepcidin expression. Dcytb, DMT1, Ireg1 and transferrin receptor 1 mRNA expression in the spleen and liver of mice treated with PHZ responded to the enhanced iron demand associated with the resulting stimulation of erythropoiesis. Enhanced iron absorption observed in PHZ-treated animals is facilitated by the up-regulation of the genes involved in iron transport and recycling. The probable association of the erythroid and the store regulators of iron homeostasis and absorption in the mice is discussed.

Animals↗
PubMed2004

Effect of altered iron metabolism on markers of haem biosynthesis and intestinal iron absorption in mice.

In this study, well-characterised animal models of altered iron metabolism were used to investigate link(s) between haem biosynthesis and intestinal iron absorption. Mice rendered iron deficient by feeding a low-iron diet for 3-4 weeks showed low levels of hepatic non-haem iron and hepcidin mRNA, with reduced urinary 5-aminolaevulinic acid (ALA) excretion and enhanced intestinal iron absorption. Hepatic ALA synthase activity was reduced while ALA dehydratase activity was increased. Iron-loaded mice had markedly increased liver non-haem iron and hepcidin mRNA, with increased urinary ALA excretion. Intestinal iron absorption was decreased mainly due to a reduction in transfer of absorbed iron from mucosa to the carcass. Hepatic ALA synthase activity was increased and ALA dehydratase activity moderately reduced. Mice exposed to hypoxia (0.5 atm) for 1-3 days had reduced hepatic hepcidin mRNA and urinary ALA excretion, while intestinal iron absorption was increased. Hepatic ALA synthase activity was reduced. The ALA dehydratase activity in liver and spleen was markedly enhanced. Injection of ALA to iron-deficient mice or hypoxic mice reduced their intestinal iron absorption to normal levels. This study further supports the hypothesis that alterations in haem biosynthesis influence duodenal iron absorption. ALA in particular appears to function as a modulator in controlling intestinal iron absorption.

5-Aminolevulinate Synthetase↗
PubMed2004

Effect of transition metal ions (cobalt and nickel chlorides) on intestinal iron absorption.

BACKGROUND: Haem biosynthesis may regulate intestinal iron absorption through changes in cellular levels of delta-aminolaevulinic acid (ALA), haem and perhaps other intermediates. CoCl2 and NiCl2 are activators of haem oxygenase, the rate-limiting enzyme in haem catabolism. Co2+ and Ni2+ may also regulate and increase iron absorption through a mechanism that simulates hypoxic conditions in the tissues. DESIGN: We assayed intestinal iron absorption in mice dosed with CoCl2 or NiCl2. The effects of these metal ions on splenic and hepatic levels of ALA synthase and dehydratase as well as urinary levels of ALA and phosphobilinogen were also assayed. RESULTS: While Co2+ enhanced iron absorption when administered to mice at doses of 65, 125 and 250 micromoles kg(-1) body weight, Ni2+ was effective only at the highest dose. Ni2+ but not Co2+ at the highest dose reduced urinary ALA in the treated mice. Both metals ions increased splenic expression of haem oxygenase 1 and iron regulated protein 1, proteins involved, respectively, in haem degradation and iron efflux. Co2+ induced erythropoietin expression. CONCLUSIONS: The data suggest that while the effect of Ni2+ on iron absorption could be explained by effects on ALA, the effect of Co2+ may not be explained simply by changes in haem metabolism; therefore, effects mediated by alterations of specific haemoproteins by mechanisms that simulate tissue hypoxia could be important.

Animals↗
PubMed2002

Molecular evidence for the role of a ferric reductase in iron transport.

Duodenal cytochrome b (Dcytb) is a haem protein similar to the cytochrome b561 protein family. Dcytb is highly expressed in duodenal brush-border membrane and is implicated in dietary iron absorption by reducing dietary ferric iron to the ferrous form for transport via Nramp2/DCT1 (divalent-cation transporter 1)/DMT1 (divalent metal-transporter 1). The protein is expressed in other tissues and may account for ferric reductase activity at other sites in the body.

Biological Transport↗
PubMed2001

An iron-regulated ferric reductase associated with the absorption of dietary iron.

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.

Amino Acid Sequence↗
PubMed1998

On the methods for studying the mechanisms and bioavailability of iron.

Studies of the molecular mechanisms involved in the absorption and bioavailability of iron are important to attempts made worldwide to control the high incidence of iron-associated disorders. The ultimate objective of these studies is to develop methods that are relevant to iron bioavailability and interactions in humans. However, a comprehensive understanding of the chemical and physiologic mechanisms that influence iron bioavailability is necessary to achieve this goal. Initial studies using in vitro and animal models offer the potential for flexibility and manipulation of experimental variables that could provide valuable information toward the understanding and improvement of food iron bioavailability.

Animals↗
PubMed1992

Iron deficiency and immune responses.

Iron deficiency is often associated with the impairment of the immune system, particularly the functioning of T-cell lymphocytes. Studies were therefore carried out in mice to investigate the involvement of iron in T-cell functions. Iron deficiency in mice was induced nutritionally by feeding diets differing in iron content for 4 weeks to produce normal, moderately low and severely low haematological indices. The proliferation of lymphocytes stimulated by Con A from these groups of mice was significantly affected by the degree of iron deficiency. Iron depletion also resulted in decreased production of interleukin 2 (IL-2) in the proliferating cells. The implications of these findings in the manifestation of iron deficiency anaemia are discussed.

Animals↗
PubMed1986

Pigeon (Columba L.) meat iron solubility and availability for absorption in rats.

1. The distribution of iron in 59Fe-labelled pigeon (Columba L.) leg and breast muscle and liver were determined by gel filtration. While the insoluble Fe was between 14 and 25% of the total Fe from the tissues, the haem-Fe represented 79.1% (breast) to 45% (liver) of the total Fe and ferritin was between 5.5% (breast) and 26.5% (liver) of the total Fe. 2. The tissue haem-Fe concentration was found to be lower than that determined by gel filtration using the method of Schricker et al. (1982) for non-haem-Fe and obtaining haem-Fe by difference. 3. A simulated in vitro digestion procedure showed significantly (P less than 0.01) reduced 59Fe solubility from 59Fe-labelled pigeon meat after cooking at 90 degrees for 30 min. 4. 59Fe absorption from whole pigeon meat and soluble extract was significantly reduced by cooking when given to Fe-replete rats. Cooking liver, however, slightly improved 59Fe absorption in Fe-replete rats. 5. 59Fe absorption from the separated pigeon-meat fractions (haemoproteins, ferritin and haemosiderin) was variable but considerably lower than that from whole meat. 6. The relative distribution of Fe compounds in meat, the processing conditions they are subjected to and the protein content and composition may all influence the absorption of meat-Fe to some degree.

Absorption↗
PubMed1986

Effect of soya-bean protein on meat iron solubility and absorption in rats.

1. Soya-bean proteins were used to replace 30 and 50% of the protein from 59Fe-labelled pigeon (Columba L.) and chicken meat, and the solubility of the meat 59Fe in vitro and its absorption in vivo in rats in the presence and absence of soya-bean proteins were measured. 2. Replacement of part of the chicken meat by soya-bean proteins reduced 59Fe solubility from chicken meat at all stages during simulated in vitro digestion. 3. 59Fe absorption from 59Fe-labelled chicken meat when given to both Fe-replete and Fe-deficient rats was reduced in the presence of soya-bean proteins but was unaffected by the presence of casein or bovine serum albumin. 59Fe-absorption from pigeon meat in the presence of soya-bean proteins was not reduced to the same extent as that from chicken meat. 4. There was no significant effect of soya-bean proteins on 59Fe-labelled haemoglobin Fe absorption in vivo in Fe-replete rats. 5. Absorption of 59Fe from the isolated haemoproteins from chicken meat was unaffected by soya-bean proteins but 59Fe absorption from the main non-haem-Fe fractions was strongly inhibited, particularly from haemosiderin.

Absorption↗
PubMedDate not supplied

Molecular and functional roles of duodenal cytochrome B (Dcytb) in iron metabolism.

Dcytb has been identified as the mammalian transplasma ferric reductase that catalyzes the reduction of ferric to ferrous iron in the process of iron absorption. Its mRNA and protein levels are up-regulated by several independent stimulators of iron absorption. Furthermore, its cDNA encodes putative binding sites for heme and ascorbic acid. Using Northern and Western blots, RT-PCR and confocal microscopy, we studied the expression and localisation of Dcytb in cell lines and tissues of CD1 mice. Dcytb expression and function were modulated by iron. Dcytb and DMT1, both predominantly localised in the apical region of the duodenum were up-regulated in iron deficiency. Dcytb, the iron regulated ferric reductase may also utilize cytoplasmic ascorbate as electron donor for transmembrane reduction of iron. Dcytb expression was found in other tissues apart from the duodenum and its regulation and functions at these other sites are of interest in iron metabolism.

Ascorbic Acid↗