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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Manganese transport into the blood can result from inhaling metal-containing particles. Intestinal manganese and iron absorption is mediated by divalent metal transporter 1 (DMT1) and is upregulated in iron deficiency. Since iron status alters absorption of Fe and Mn in the gut, we tested the hypothesis that iron status may alter pulmonary transport of these metals. DMT1 expression in the lungs was evaluated to explore its role in metal transport. The pharmacokinetics of intratracheally instilled 54Mn or 59Fe in repeatedly bled or iron oxide-exposed rats were compared with controls. Iron oxide exposure caused a reduction in pulmonary transport of 54Mn and 59Fe, and decreased uptake in other major organs. Low iron status from repeated bleeding also reduced pulmonary transport of iron but not of manganese. However, uptake of manganese in the brain and of iron in the spleen increased in bled rats. DMT1 transcripts were detected in airway epithelium, alveolar macrophages, and bronchial-associated lymphoid tissue in all rats. Focal increases were seen in particle-containing macrophages and adjacent epithelial cells, but no change was observed in bled rats. Although lung DMT1 expression did not correlate with iron status, differences in pharmacokinetics of instilled metals suggest that their potential toxicity can be modified by iron status.
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PMID:Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe. 1634 1

Pathways mediating pulmonary metal uptake remain unknown. Because absorption of iron and manganese could involve similar mechanisms, transferrin (Tf) and transferrin receptor (TfR) expression in rat lungs was examined. Tf mRNA was detected in bronchial epithelium, type II alveolar cells, macrophages, and bronchus-associated lymphoid tissue (BALT). Tf protein levels in lung and bronchoalveolar lavage fluid did not change in iron deficiency despite increased plasma levels, suggesting that lung Tf concentrations are regulated by local synthesis in a manner independent of body iron status. Iron oxide exposure upregulated Tf mRNA in bronchial and alveolar epithelium, macrophages, and BALT, but protein was not significantly increased. In contrast, TfR mRNA and protein were both upregulated by iron deficiency. To examine potential interactions with lung Tf, rats were intratracheally instilled with (54)Mn or (59)Fe. Unlike (59)Fe, interactions between (54)Mn and Tf in lung fluid were not detected. Absorption of intratracheally instilled (54)Mn from the lungs to the blood was unimpaired in Belgrade rats homozygous for the functionally defective G185R allele of divalent metal transporter-1, indicating that this transporter is also not involved in pulmonary manganese absorption. Pharmacological studies of (54)Mn uptake by A549 cells suggest that metal uptake by type II alveolar epithelial cells is associated with activities of both L-type Ca(2+) channels and TRPM7, a member of the transient receptor potential melastatin subfamily. These results demonstrate that iron and manganese are absorbed by the pulmonary epithelium through different pathways and reveal the potential role for nonselective calcium channels in lung metal clearance.
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PMID:Manganese and iron transport across pulmonary epithelium. 1642 68

Manganese (Mn) is an essential trace element, though at elevated exposures it is also a neurotoxicant. Several mechanisms underlying manganese toxicity have been investigated, although a consistent mechanism(s) of action at low exposures has not been fully elucidated. Here we systematically evaluated the effects of in vitro manganese exposure on intracellular iron (Fe) homeostasis and iron-regulatory protein (IRP) binding activity in undifferentiated PC12 cells over a range of manganese exposure concentrations (1, 10, 50, and 200 microM MnCl(2)) and exposure durations (12, 24, 36, and 48 hr), to test the hypothesis that moderately elevated manganese exposure disrupts cellular iron regulation. Results demonstrate that manganese exposure produces a rapid and sustained dose-dependent dysregulation of cellular iron metabolism, with effects occurring as early as 12 hr exposure and at manganese doses as low as 1 microM. Manganese exposure altered the dynamics of IRP-1 binding and the intracellular abundance of IRP-2, and altered the cellular abundance of transferrin receptor, ferritin, and mitochondrial aconitase protein levels. Cellular levels of labile iron were significantly increased with manganese exposure, although total cellular iron levels were not. The overall pattern of effects shows that manganese produced an inappropriate cellular response akin to iron deficiency, to which the cells were able to mount a compensatory response. Consistent with our previous studies, these data indicate that even low to moderate exposures to Manganese in vitro significantly disrupt cellular iron metabolism, which may be an important contributory mechanism of manganese neurotoxicity.
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PMID:Temporal responses in the disruption of iron regulation by manganese. 1656 77

Manganese (Mn), an element found in many foods, is an important and essential nutrient for proper health and maintenance. It is toxic in high doses, however, and exposure to excessive levels can result in the onset of a neurological disorder similar to, but distinct from, Parkinson's disease. Historically, Mn neurotoxicity was most commonly associated with various occupations, such as Mn mining, welding and steel production. More recently, increases in both blood and brain Mn levels have been observed in persons with liver disease or those receiving prolonged parenteral nutrition. Additionally, rodent data suggest that iron deficiency and anemia may be risk factors for Mn neurotoxicity. Clinically, brain Mn accumulation can be monitored in vivo using non-invasive magnetic resonance imaging (MRI) due to the paramagnetic nature of this element. Indeed, MRI has been used in a variety of settings to evaluate the brain Mn deposition in various populations. This review focuses on the use of MRI technology in studies related specifically to Mn neurotoxicity. Thus, we will examine reports using MRI to confirm brain Mn accumulation in human populations, and conclude with data from non-human primate and rodent models of Mn neurotoxicity.
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PMID:The use of magnetic resonance imaging (MRI) in the study of manganese neurotoxicity. 1662 Sep 89

Iron (Fe) is an essential trace metal involved in numerous cellular processes. Iron deficiency (ID) is reported as the most prevalent nutritional problem worldwide. Increasing evidence suggests that ID is associated with altered neurotransmitter metabolism and a risk factor for manganese (Mn) neurotoxicity. Though recent studies have established differences in which the female brain responds to ID-related neurochemical alterations versus the male brain, little is known about the interactions of dietary ID, Mn exposure, and sex on gamma-amino butyric acid (GABA). Male and female Sprague-Dawley rats were randomly divided into four dietary treatment groups: control (CN), control/Mn supplemented, ID, and ID/Mn supplemented. After 6 weeks of treatment, both ID diets caused a highly significant decrease in Fe concentrations across all brain regions compared to CN in both sexes. Both ID and Mn supplementation led to significant accumulation of Mn across all brain regions in both sexes. There was no main effect of sex on Fe or Mn accumulation. Striatal synaptosomes were utilized to examine the effect of dietary intervention on (3)H-GABA uptake. At 4 weeks, there was a significant correlation between Fe concentration and (3)H-GABA uptake in male rats (p < 0.05). At 6 weeks, there was a significant inverse correlation between Mn concentration and (3)H-GABA uptake in male and female rats and a postitive correlation between Fe concentration and (3)H-GABA uptake in female rats (p < 0.05). In conclusion, ID-associated Mn accumulation is similar in both sexes, with Mn levels affecting GABA uptake in both sexes in a comparable fashion.
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PMID:Brain manganese accumulation is inversely related to gamma-amino butyric acid uptake in male and female rats. 1703 2

The objective of this update is to give an overview of the effects of dietary nutrients on the structure and certain functions of the brain. As any other organ, the brain is elaborated from substances present in the diet (sometimes exclusively, for vitamins, minerals, essential amino-acids and essential fatty acids, including omega- 3 polyunsaturated fatty acids). However, for long it was not fully accepted that food can have an influence on brain structure, and thus on its function, including cognitive and intellectuals. In fact, most micronutrients (vitamins and trace-elements) have been directly evaluated in the setting of cerebral functioning. For instance, to produce energy, the use of glucose by nervous tissue implies the presence of vitamin B1; this vitamin modulates cognitive performance, especially in the elderly. Vitamin B9 preserves brain during its development and memory during ageing. Vitamin B6 is likely to benefit in treating premenstrual depression. Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters. Vitamin B12 delays the onset of signs of dementia (and blood abnormalities), provided it is administered in a precise clinical timing window, before the onset of the first symptoms. Supplementation with cobalamin improves cerebral and cognitive functions in the elderly; it frequently improves the functioning of factors related to the frontal lobe, as well as the language function of those with cognitive disorders. Adolescents who have a borderline level of vitamin B12 develop signs of cognitive changes. In the brain, the nerve endings contain the highest concentrations of vitamin C in the human body (after the suprarenal glands). Vitamin D (or certain of its analogues) could be of interest in the prevention of various aspects of neurodegenerative or neuroimmune diseases. Among the various vitamin E components (tocopherols and tocotrienols), only alpha-tocopherol is actively uptaken by the brain and is directly involved in nervous membranes protection. Even vitamin K has been involved in nervous tissue biochemistry. Iron is necessary to ensure oxygenation and to produce energy in the cerebral parenchyma (via cytochrome oxidase), and for the synthesis of neurotransmitters and myelin; iron deficiency is found in children with attention-deficit/hyperactivity disorder. Iron concentrations in the umbilical artery are critical during the development of the foetus, and in relation with the IQ in the child; infantile anaemia with its associated iron deficiency is linked to perturbation of the development of cognitive functions. Iron deficiency anaemia is common, particularly in women, and is associated, for instance, with apathy, depression and rapid fatigue when exercising. Lithium importance, at least in psychiatry, is known for a long time. Magnesium plays important roles in all the major metabolisms: in oxidation-reduction and in ionic regulation, among others. Zinc participates among others in the perception of taste. An unbalanced copper metabolism homeostasis (due to dietary deficiency) could be linked to Alzheimer disease. The iodine provided by the thyroid hormone ensures the energy metabolism of the cerebral cells; the dietary reduction of iodine during pregnancy induces severe cerebral dysfunction, actually leading to cretinism. Among many mechanisms, manganese, copper, and zinc participate in enzymatic mechanisms that protect against free radicals, toxic derivatives of oxygen. More specifically, the full genetic potential of the child for physical growth ad mental development may be compromised due to deficiency (even subclinical) of micronutrients. Children and adolescents with poor nutritional status are exposed to alterations of mental and behavioural functions that can be corrected by dietary measures, but only to certain extend. Indeed, nutrient composition and meal pattern can exert either immediate or long-term effects, beneficial or adverse. Brain diseases during aging can also be due to failure for protective mechanism, due to dietary deficiencies, for instance in anti-oxidants and nutrients (trace elements, vitamins, non essential micronutrients such as polyphenols) related with protection against free radicals. Macronutrients are presented in the accompanying paper.
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PMID:Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. 1706 9

Welders can be exposed to high levels of manganese through welding fumes. Although it has already been suggested that excessive manganese exposure causes neurotoxicity, called manganism, the pathway of manganese transport to the brain with welding-fume exposure remains unclear. Iron is an essential metal that maintains a homeostasis in the body. The divalent metal transporter 1 (DMT1) transports iron and other divalent metals, such as manganese, and the depletion of iron is known to upregulate DMT1 expression. Accordingly, this study investigated the tissue distribution of manganese in iron-sufficient and iron-deficient rats after welding-fume exposure. The feeding of an iron-deficient diet for 4 wk produced a depletion of body iron, such as decreased iron levels in the serum and tissues, and upregulated the DMT1 expression in the rat duodenum. The iron-sufficient and iron-deficient rats were then exposed to welding fumes generated from manual metal arc stainless steel at a concentration of 63.5 +/- 2.3 mg/m3 for 2 h per day over a 30-day period. Animals were sacrificed on days 1, 15, and 30. The level of body iron in the iron-deficient rats was restored to the control level after the welding-fume exposure. However, the tissue distributions of manganese after the welding-fume exposure showed similar patterns in both the iron-sufficient and iron-deficient groups. The concentration of manganese increased in the lungs and liver on days 15 and 30, and increased in the olfactory bulb on day 30. Slight and heterogeneous increases of manganese were observed in different brain regions. Consequently, these findings suggest that the presence of Fe in the inhaled welding fumes may not have a significant effect on the uptake of Mn into the brain. Thus, the condition of iron deficiency did not seem to have any apparent effect on the transport of Mn into the brain after the inhalation of welding fumes.
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PMID:Tissue distribution of manganese in iron-sufficient or iron-deficient rats after stainless steel welding-fume exposure. 1749 34

Previously, we had identified FOX1 and FTR1 as iron deficiency-inducible components of a high-affinity copper-dependent iron uptake pathway in Chlamydomonas. In this work, we survey the version 3.0 draft genome to identify a ferrireductase, FRE1, and two ZIP family proteins, IRT1 and IRT2, as candidate ferrous transporters based on their increased expression in iron-deficient versus iron-replete cells. In a parallel proteomic approach, we identified FEA1 and FEA2 as the major proteins secreted by iron-deficient Chlamydomonas reinhardtii. The recovery of FEA1 and FEA2 from the medium of Chlamydomonas strain CC425 cultures is strictly correlated with iron nutrition status, and the accumulation of the corresponding mRNAs parallels that of the Chlamydomonas FOX1 and FTR1 mRNAs, although the magnitude of regulation is more dramatic for the FEA genes. Like the FOX1 and FTR1 genes, the FEA genes do not respond to copper, zinc, or manganese deficiency. The 5' flanking untranscribed sequences from the FEA1, FTR1, and FOX1 genes confer iron deficiency-dependent expression of ARS2, suggesting that the iron assimilation pathway is under transcriptional control by iron nutrition. Genetic analysis suggests that the secreted proteins FEA1 and FEA2 facilitate high-affinity iron uptake, perhaps by concentrating iron in the vicinity of the cell. Homologues of FEA1 and FRE1 were identified previously as high-CO(2)-responsive genes, HCR1 and HCR2, in Chlorococcum littorale, suggesting that components of the iron assimilation pathway are responsive to carbon nutrition. These iron response components are placed in a proposed iron assimilation pathway for Chlamydomonas.
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PMID:FEA1, FEA2, and FRE1, encoding two homologous secreted proteins and a candidate ferrireductase, are expressed coordinately with FOX1 and FTR1 in iron-deficient Chlamydomonas reinhardtii. 1766 Mar 59

Manganese (Mn) deficiency is an important plant nutritional disorder in many parts of the world. Barley (Hordeum vulgare) genotypes differ considerably in their ability to grow in soils with low Mn(2+) availability. Differential genotypic Mn efficiency can be attributed to differences in Mn(2+) uptake kinetics in the low nanomolar concentration range. However, the molecular basis for these differences has not yet been clarified. We present here the identification and characterization of the first barley gene encoding a plasma membrane-localized metal transport protein able to transport Mn(2+). The gene is designated HvIRT1 (for IRON-REGULATED TRANSPORTER1) because it belongs to the ZIP gene family and has a high similarity to rice (Oryza sativa) OsIRT1. A novel yeast uptake assay based on inductively coupled plasma-mass spectrometry analysis of 31 different metal and metalloid ions showed that the HvIRT1 protein, in addition to Mn(2+), also transported Fe(2+)/Fe(3+), Zn(2+), and Cd(2+). Both Mn and iron deficiency induced an up-regulation of HvIRT1 in two barley genotypes differing in Mn efficiency, but the expression levels in all cases were highest (up to 40%) in the Mn-efficient genotype. The higher expression of HvIRT1 correlated with an increased Mn(2+) uptake rate. We conclude that HvIRT1 is an important component controlling Mn(2+) uptake in barley roots and contributes to genotypic differences in Mn(2+) uptake kinetics.
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PMID:Manganese efficiency in barley: identification and characterization of the metal ion transporter HvIRT1. 1861 14

Unlike other essential trace elements (e.g., zinc and iron) it is the toxicity of manganese (Mn) that is more common in human populations than its deficiency. Data suggest alterations in dopamine biology may drive the effects associated with Mn neurotoxicity, though recently gamma-aminobutyric acid (GABA) has been implicated. In addition, iron deficiency (ID), a common nutritional problem, may cause disturbances in neurochemistry by facilitating accumulation of Mn in the brain. Previous data from our lab have shown decreased brain tissue levels of GABA as well as decreased (3)H-GABA uptake in synaptosomes as a result of Mn exposure and ID. These results indicate a possible increase in the concentration of extracellular GABA due to alterations in expression of GABA transport and receptor proteins. In this study weanling-male Sprague-Dawley rats were randomly placed into one of four dietary treatment groups: control (CN; 35mg Fe/kg diet), iron-deficient (ID; 6mg Fe/kg diet), CN with Mn supplementation (via the drinking water; 1g Mn/l) (CNMn), and ID with Mn supplementation (IDMn). Using in vivo microdialysis, an increase in extracellular GABA concentrations in the striatum was observed in response to Mn exposure and ID although correlational analysis reveals that extracellular GABA is related more to extracellular iron levels and not Mn. A diverse effect of Mn exposure and ID was observed in the regions examined via Western blot and RT-PCR analysis, with effects on mRNA and protein expression of GAT-1, GABA(A), and GABA(B) differing between and within the regions examined. For example, Mn exposure reduced GAT-1 protein expression by approximately 50% in the substantia nigra, while increasing mRNA expression approximately four-fold, while in the caudate putamen mRNA expression was decreased with no effect on protein expression. These data suggest that Mn exposure results in an increase in extracellular GABA concentrations via altered expression of transport and receptor proteins, which may be the basis of the neurological characteristics of manganism.
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PMID:Manganese exposure alters extracellular GABA, GABA receptor and transporter protein and mRNA levels in the developing rat brain. 1877 89


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