RESUMO
Copper (Cu) is an essential element for plants, especially in photosynthesis, as it is required for plastocyanin function in electron transfer reactions at thylakoid membranes. In Arabidopsis thaliana, Cu deficiency leads to the Cu economy response, in which plants prioritize Cu usage by plastocyanin in detriment of non-essential cupric proteins. In rice (Oryza sativa), however, this response has not been characterized. Rice OsHMA5 is a Cu xylem-loading transporter involved in Cu translocation from roots to shoots, as suggested by the analysis of oshma5 mutant plants. Aiming to understand how rice plants respond to Cu deficiency and how decreased Cu translocation to shoots can affect this response, we characterized the physiological and molecular responses of WT and oshma5 plants under control and Cu deficiency treatments. We found evidence that shoots of oshma5 plants are more prone to Cu deficiency compared to shoots of WT plants, as demonstrated by decreased chlorophyll and Cu concentrations, and electron transport rate. Gene expression analysis revealed that Cu high-affinity transporters OsCOPT1 and OsCOPT5, along with a set of miRNAs and three Cu/Zn superoxide dismutases are responsive to Cu deficiency in both WT and oshma5 plants, suggesting their involvement in the Cu economy response. However, Fe superoxide dismutase was not up-regulated in rice, indicating a difference compared to the A. thaliana Cu economy model. Therefore, we provide evidence for a partially conserved Cu economy response in rice, in comparison to A. thaliana.
Assuntos
Cobre/fisiologia , Oryza/fisiologia , Proteínas de Plantas/fisiologia , Arabidopsis/fisiologia , Regulação da Expressão Gênica de PlantasRESUMO
Requirements for optimal nutrition, especially for micronutrients, are not well defined for premature infants. The "reference fetus," developed by Ziegler et al,(1) has served as a model to define nutritional needs and studies designed to determine nutrient requirements. Revision of nutrient requirements and provision of optimal nutrition may lead to improved outcomes in preterm infants. Appropriate provision of nutrients also may help prevent nutritional disorders, such as metabolic bone disease and anemia. In this review, we discuss calcium, phosphorus, magnesium, vitamin D, iron, and copper, and define optimal intakes based on the available published data.
Assuntos
Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido Prematuro/fisiologia , Micronutrientes/fisiologia , Necessidades Nutricionais/fisiologia , Cálcio da Dieta/administração & dosagem , Cálcio da Dieta/metabolismo , Cobre/administração & dosagem , Cobre/fisiologia , Dieta , Suplementos Nutricionais , Humanos , Recém-Nascido , Ferro da Dieta/administração & dosagem , Ferro da Dieta/metabolismo , Magnésio/administração & dosagem , Magnésio/fisiologia , Micronutrientes/administração & dosagem , Fósforo na Dieta/administração & dosagem , Fósforo na Dieta/metabolismo , Vitamina D/administração & dosagem , Vitamina D/fisiologiaRESUMO
Deficiencies of nutrients such as amino acids, vitamins, lipids, and trace elements during gestation and early infanthood have strong deleterious effects on the development of the limbic system; these effects may be irreversible, even when adequate supplementation is provided at later developmental stages. Recent advances in the neurochemistry of biometals are increasingly establishing the roles of the trace elements iron, copper, zinc, and selenium in a variety of cell functions and are providing insight into the repercussions of deficiencies and excesses of these elements on the development of the central nervous system, especially the limbic system. The limbic system comprises diverse areas with high metabolic demands and differential storage of iron, copper, zinc, and selenium. This review summarizes available evidence suggesting the involvement of these trace elements in pathological disorders of the limbic system.
Assuntos
Encefalopatias/etiologia , Sistema Límbico/efeitos dos fármacos , Sistema Límbico/crescimento & desenvolvimento , Oligoelementos/sangue , Oligoelementos/deficiência , Encefalopatias/sangue , Cobre/sangue , Cobre/deficiência , Cobre/fisiologia , Humanos , Ferro/sangue , Ferro/fisiologia , Deficiências de Ferro , Sistema Límbico/fisiologia , Fenômenos Fisiológicos da Nutrição/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição/fisiologia , Necessidades Nutricionais , Selênio/sangue , Selênio/deficiência , Selênio/fisiologia , Zinco/sangue , Zinco/deficiência , Zinco/fisiologiaRESUMO
Copper is an essential micronutrient involved in a variety of biological processes indispensable to sustain life. At the same time, it can be toxic when present in excess, the most noticeable chronic effect being liver damage. Potent, efficient regulatory mechanisms control copper absorption in the digestive tract and copper biliary excretion; absorption ranges between 12 and 60% in humans, depending on Cu intake, presence of other factors in the diet that may promote or inhibit its absorption and on the copper status of the individual. Current evidence suggests that copper deficiency may be more prevalent than previously thought, while copper toxicity is uncommon under customary daily life conditions. Menkes syndrome and Wilson disease are genetic conditions associated with severe copper deficiency and severe copper toxicity, respectively. Effects of milder degrees of copper deficiency and excess copper exposure are not well described, mainly due to lack of sensitive and specific indicators; serum copper concentration and ceruloplasmin are the most frequently used indicators, but they only detect rather intense changes of copper status. Of the many proteins assessed as potential markers of copper status the chaperone of Zn-Cu superoxide dismutase (CCS1) has yielded promising results; data on its performance under different conditions are needed to confirm its use as an indicator of early copper deficiency. Defining copper requirements and upper safe limits of consumption (UL) is a complex process since there are adverse health consequences from both copper deficiency and copper excess (U shape curve). The regulatory framework for risk assessment of essential trace elements introduced by the International Programme on Chemical Safety (IPCS) has proposed a homeostatic model to determine the Adequate Range of Oral Intake (AROI) of essential trace elements; the nadir of the resulting U shape curve serves to define the AROI. At this range of intake physiological mechanisms allow for normal homeostasis and basically, there are no detectable adverse effects. At present, Recommended Dietary Intakes (DRIs) and Adequate Intakes (AIs) are used to recommend copper intakes at different ages and life situations. Evidence obtained in humans and non-human primates presented here suggest that current copper UL should be re evaluated. Developing the scientific basis for a copper UL and evaluating the relevance of copper deficiency globally are future key challenges for copper researchers.
Assuntos
Cobre/fisiologia , Homeostase , Biomarcadores , Criança , Cobre/deficiência , Cobre/toxicidade , HumanosRESUMO
Iron deficiency is prevalent in most of the developing world where it coexists with other micronutrient deficiencies such as copper. Combined supplementation with iron and copper is one of the strategies that can be used to improve the iron and copper status of a population. However, there is concern about potential negative interactions between these two micronutrients due to a competitive binding to the divalent metal transporter 1 (DMTl), a proton-coupled transporter of a variety of divalent metals including copper. The aim of this study was to measure the effect of daily supplementation with 8 mg of copper, as copper sulfate during 6 months on the iron status. Sixty healthy male adults were randomized to receive a copper supplement or a placebo. Fasting blood samples were obtained before and after copper supplementation to evaluate the iron and copper nutritional status. Copper supplementation did not change significantly iron and copper status parameters. In conclusion, daily supplementation with 8 mg of copper during 6 months does not deteriorate iron nutrition in adult men.
La deficiencia de hierro coexiste con otras carencias, entre ellas de cobre. La suplementación combinada con estos nutrientes es una de las estrategias utilizadas en su prevención. Sin embargo, existe la posibilidad de interacciones negativas, ya que el DMT1, principal transportador de hierro no hem a nivel intestinal, también transporta cobre. El propósito del estudio fue medir el efecto de la suplementación con 8 mg diarios de cobre, como sulfato de cobre, durante 6 meses, sobre la nutrición de hierro. Sesenta hombres adultos, aparentemente sanos, fueron seleccionados al azar para recibir el suplemento de cobre o un placebo. Se tomaron muestras de sangre en ayunas antes y después de finalizada la suplementacion para evaluar la nutrición de hierro y de cobre. La suplementacion con cobre no determinó cambios significativos en los indicadores de nutrición de cobre y de hierro. En conclusión, la suplementacion con 8 mg diarios de Cu administrado entre comidas durante 6 meses no deterioró la nutrición de hierro en hombres adultos.
Assuntos
Humanos , Masculino , Cobre/administração & dosagem , Cobre/fisiologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Ferro/fisiologia , Suplementos Nutricionais , Método Duplo-Cego , Deficiências de Ferro/prevenção & controle , Proteínas de Transporte de Cátions/fisiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Copper is essential for proper functioning of cytochrome c oxidases, and therefore for cellular respiration in eukaryotes and many bacteria. Here we show that a new periplasmic protein (PCu(A)C) selectively inserts Cu(I) ions into subunit II of Thermus thermophilus ba(3) oxidase to generate a native Cu(A) site. The purported metallochaperone Sco1 is unable to deliver copper ions; instead, it works as a thiol-disulfide reductase to maintain the correct oxidation state of the Cu(A) cysteine ligands.
Assuntos
Cobre , Complexo IV da Cadeia de Transporte de Elétrons/fisiologia , Thermus thermophilus/enzimologia , Cobre/fisiologia , Modelos Moleculares , OxirreduçãoRESUMO
Previous studies showed that responses to chronic administration of copper were significantly associated with gender, raising the need to better characterize the relation between the effects observed and stradiols. The objective of this study was to measure copper and liver function indicators and the sex hormone binding globulin (SHBG) serum concentrations in healthy adults exposed to copper, grouped by sex and phase of the female hormonal cycle. Healthy females on day 7 (follicular phase, Group 1, n = 39), on day 21 (secretory phase, Group 2, n = 34) and males (comparison group, Group 3, n = 34) received 8 mg Cu/day (as copper sulfate), orally, for 6 months. On days 0, 30, 60, 120, and 180, the serum concentration of copper, ceruloplasmin, liver aminotransferases, and SHBG were measured. Analysis of results included analysis of variance (ANOVA; repeated measures) and the post hoc Bonferroni correction. Participants remained healthy throughout the study period, including aminotransferases below the cut off in all measures. GGT, AST, and ALT activities were significantly different by group and by time (ANOVA repeated measures P < 0.05). Six-month curves of serum copper and ceruloplasmin concentrations were different by group, by time and interaction group x time (all P < 0.001). SHBG curves were different by group and time (P < 0.01), and interaction group x time (P < 0.009). Serum copper, ceruloplasmin, and liver aminotranferases are influenced by estrogens/progesterone, something that should be considered when these indicators are used as outcomes of effects. Time of sampling was also significantly associated with the indicators and deserves further study.
Assuntos
Cobre/fisiologia , Fígado/fisiologia , Ciclo Menstrual/fisiologia , Globulina de Ligação a Hormônio Sexual/metabolismo , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Ceruloplasmina/metabolismo , Cobre/sangue , Estrogênios/sangue , Feminino , Humanos , Masculino , Progesterona/sangue , gama-Glutamiltransferase/sangueRESUMO
Microminerals including copper and iron are essential to immunity and health in human beings. The development of powerful tools in analytical cell biology and molecular genetics has facilitated efforts to identify specific cellular and molecular functions of trace elements in the maturation, activation and functions of host defence mechanisms. Selected recent reports about the role of copper and iron nutrition on immune functions are critically analysed here. Effects of trace element supplementation on infectious morbidity are also reviewed. While micromineral deficiencies, in general, may have widespread effects on nearly all components of immune response, these effects can be reversed by supplementation. However, the conflicting effects of iron deficiency and iron supplementation in vitro on the defensive systems reveals the urgent need for further additional information on the in vivo situation. In the elderly, vaccination against respiratory infections is likely to protect only 30-70% of the population. However, it may be possible to modulate immune function and ultimately reduce the severity of infections through micronutrient supplementation. Thus, microminerals contribute to the maintenance of the balance between immunity and health in humans.
Assuntos
Cobre/fisiologia , Imunocompetência/fisiologia , Ferro/fisiologia , Animais , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/terapia , Cobre/imunologia , Suplementos Nutricionais , Humanos , Imunidade Celular/fisiologia , Ferro/imunologia , CamundongosAssuntos
Animais , Cobre/fisiologia , Cobre/metabolismo , Ferro/fisiologia , Ferro/metabolismo , Congresso , MetaisRESUMO
BACKGROUND: Copper (Cu) is an essential trace element for many biological processes including maintenance of both innate and acquired branches of immunity. OBJECTIVE: To measure the effect of copper supplementation on IL-2 and TNF-alpha production in subjects with lower and higher ceuloplasmin (Cp) values within normal range. DESIGN: Healthy adults (17 men and 16 women) with normal-low (low Cp) and normal-high Cp (high Cp) values were supplemented with 10 mg Cu/day (as CuSO(4)) during 2 months. METHOD: Before and after supplementation blood mononuclear cells were incubated in the absence or presence of phytohaemagglutinin or lipopolysaccharide for induction of IL-2 and TNF-alpha, respectively. The secretion of cytokines was measured by ELISA. Cu supplementation did not modify classical biochemical markers of Cu status. RESULTS: After supplementation, a significant increase in IL-2 production was found only in subjects with normal-low plasma Cp. Before and after Cu supplementation geometric mean and range +/- 1 SEM values were 1,566 (1,287-1,905) and 2,514 (2,159-2,927) pg/mL, respectively (two-way ANOVA for repeated measures: Cp level p < 0.001; time = NS; interaction Cp level and time p < 0.05). We did not observe changes in TNF-alpha production after Cu supplementation. CONCLUSIONS: Cu supplementation increased secretion of IL-2 and not TNF-alpha, which suggests an activation of proliferative but not inflammatory cytokines. These results support hypothesis that IL-2 may be a good indicator to identify a subgroup of individuals (polymorphism) who differs in Cu metabolism.
Assuntos
Cobre/fisiologia , Interleucina-2/biossíntese , Adulto , Biomarcadores/sangue , Células Cultivadas , Ceruloplasmina/metabolismo , Cobre/administração & dosagem , Cobre/sangue , Sulfato de Cobre/administração & dosagem , Sulfato de Cobre/sangue , Sulfato de Cobre/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
As part of a general project aimed at elucidating the initiation of mucin-type O-glycosylation in helminth parasites, we have characterized a novel ppGalNAc-T (UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase) from the cestode Echinococcus granulosus (Eg-ppGalNAc-T1). A full-length cDNA was isolated from a library of the tissue-dwelling larval stage of the parasite, and found to code for a 654-amino-acid protein containing all the structural features of ppGalNAc-Ts. Functional characterization of a recombinant protein lacking the transmembrane domain showed maximal activity at 28 degrees C, in the range 6.5-7.5 pH units and in the presence of Cu2+. In addition, it transferred GalNAc to a broad range of substrate peptides, derived from human mucins and O-glycosylated parasite proteins, including acceptors containing only serine or only threonine residues. Interestingly, the C-terminal region of Eg-ppGalNAc-T1 bears a highly unusual lectin domain, considerably longer than the one from other members of the family, and including only one of the three ricin B repeats generally present in ppGalNAc-Ts. Furthermore, a search for conserved domains within the protein C-terminus identified a fragment showing similarity to a recently defined domain, specialized in the binding of organic phosphates (CYTH). The role of the lectin domain in the determination of the substrate specificity of these enzymes suggests that Eg-ppGalNAc-T1 would be involved in the glycosylation of a special type of substrate. Analysis of the tissue distribution by in situ hybridization and immunohistochemistry revealed that this transferase is expressed in the hydatid cyst wall and the subtegumental region of larval worms. Therefore it could participate in the biosynthesis of O-glycosylated parasite proteins exposed at the interface between E. granulosus and its hosts.
Assuntos
Echinococcus granulosus/enzimologia , Lectinas/química , N-Acetilgalactosaminiltransferases/química , Peptídeos/química , Sequência de Aminoácidos , Animais , Células COS/química , Células COS/metabolismo , Bovinos , Doenças dos Bovinos/enzimologia , Doenças dos Bovinos/parasitologia , Linhagem Celular , Chlorocebus aethiops , Clonagem Molecular , Cobre/fisiologia , DNA Complementar/genética , DNA de Helmintos/genética , Equinococose/enzimologia , Equinococose/veterinária , Proteínas de Helminto/biossíntese , Proteínas de Helminto/química , Proteínas de Helminto/genética , Proteínas de Helminto/fisiologia , Concentração de Íons de Hidrogênio , Lectinas/genética , Manganês/metabolismo , Dados de Sequência Molecular , N-Acetilgalactosaminiltransferases/biossíntese , N-Acetilgalactosaminiltransferases/genética , N-Acetilgalactosaminiltransferases/fisiologia , Peptídeos/genética , Estrutura Terciária de Proteína , Análise de Sequência de DNA , Especificidade por Substrato/genética , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
Prions are the etiological agents for infectious degenerative encephalopaties acting by inducing conformational changes in the cellular prion protein (PrPc), which is a cell membrane GPI anchored glycoprotein. Besides its conservation among species and expression in most tissues, and in particular, in high levels in the nervous system, the role for cellular prion protein remained obscure for some time. Initial skepticism about such a role was mainly due to the absence of a gross phenotype alteration in cellular prion protein null mice. In the last few years, some possible biological functions for cellular prion protein have been described. Copper binds to the molecule and the resulting complex may be responsible for cell protection against oxidative stress. Cellular prion protein is also a high-affinity ligand for laminin, and induces neuronal cell adhesion, neurite extension and maintenance. The binding site resides in a carboxy-terminal peptide of the gamma-1 chain, which is very conserved among all laminin types, indicating that this interaction may be relevant in other tissues besides the brain. Moreover, cellular prion protein association with a peptide that mimics a putative ligand at the cell surface, p66, triggers neuroprotective signals through a cAMP/PKA-dependent pathway. Since PrPc recycles from membrane to an intracellular compartment, which is induced by copper binding, it is also possible that the internalization mechanism allows switching off elicited signals.
Assuntos
Príons/fisiologia , Animais , Cobre/metabolismo , Cobre/fisiologia , Endocitose/fisiologia , Humanos , Ligantes , Memória/fisiologia , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologiaRESUMO
La deficiencia de micronutrientes es frecuente en países en desarrollo. El objetivo del estudio fué comparar los niveles séricos de zinc, hierro y cobre en tres grupos de escolares (8 a 9 años) y correlacionarlos con algunas medidas antropométricas. El grupo 1 estuvo constituido por 26 escolares de un colegio privado de Santafé de Bogotá, el 2 por 21 niños de instituciones públicas de una zona rural, cercana a esta ciudad y el 3 por 28 sujetos de una escuela pública de la capital. Los micronutrientes se midieron por espectrometria de emisión atómica con plasma acoplado por inducción. El grupo 1 presentó talla (126.2+/-3.6) mayor al 2 (122.6+/-4.8 cm) y al 3 (122.1 +/-5.0 cm). Las concentraciones de zinc del grupo 1 (67+/-9 ug/dl) fueron mayores al 2 (59+/-11 ug/dl) y al 3 (50+/-13ug/dl). El grupo 3 presentó sidermia menor (71+/-21ug/dl) al 1 (90+/-30ug/dl). El grupo 1 evidenció niveles de cobre (100+/-19Ug/dl) mayores al 2 (77+/-13ug/dl) y al 3 (82+/-20ug/dl). Los resultados suguieren que los niños de los grupos 2 y 3 están expuestos a posibles condicienes medioambientales que inciden desfavorablemente en su crecimiento corporal y que son los niños del grupo 2 los que presntan el menor acceso a los micronutrientes zinc y hierro.
Assuntos
Humanos , Pré-Escolar , Criança , Cobre/fisiologia , Ferro/sangue , Ferro/fisiologia , Oligoelementos/sangue , Oligoelementos/isolamento & purificação , Oligoelementos/fisiologia , Zinco/sangue , Zinco/fisiologiaRESUMO
Se determinaron los niveles plasmáticos del Zinc (ZN) y cobre (CU), por estrofotometría de absorción atómica, a 75 niños que asistieron al Centro Clínico Nutricional "Menca de Leoni", Caracas. Además se les determinó el estado nutricional de la composición corporal (Circunferencia del Brazo Izquierdo (CBI): área Magra (AG), categorizándose en varios niveles de adecuación. Se observó una tendencia a disminuir la concentración plasmática de Zn a medida que el estado nutricional del AM y el AG desmejora, situación que no se evidenció con la CIB. Sin embargo, se consiguió correlación positiva significativa entre los niveles de Zn y los parámetros antropométricos estudiados. En cuanto al Cu plasmático no se observó variación significativa entre las diferentes categorías del estado nutricional de la conposición corporal hecho que se evidencia al realizar el análisis de correlación. El nivel de Zn plasmático puede influir en el estado nutricional de la composición corporal, debido al efecto que éste tiene sobre el metabolismo del nitrógeno. El Cu no pareciera afectar la CBI, AM y AG
Assuntos
Masculino , Feminino , Humanos , Pré-Escolar , Lactente , Antropometria , Criança , Composição Corporal/fisiologia , Cobre/análise , Cobre/sangue , Cobre/fisiologia , Estado Nutricional/fisiologia , Espectrofotometria/estatística & dados numéricos , Zinco/análise , Zinco/sangueRESUMO
A series of reports in the 1960s highlighted nutritional copper deficiencies in infants and children recovering from malnutrition in Peru; since that time, a cascade of additional cases in premature infants, in patients receiving total parenteral nutrition, and in those receiving special diets or unmodified cow milk have been reported. The identification by Danks that Menkes syndrome, a genetically determined defect in copper absorption and utilization, is responsible for the observed clinical manifestations provided further insight into the physiopathologic effects of copper deficiency. New information on the metabolism and physiologic role of copper, plus the identification of additional copper metalloenzymes and improvement in how to determine copper status, has fueled interpretation and speculation on how and why the classic signs of copper deficiency occur, as well as on the possible effects of mild deficiencies. Also under scrutiny are potential interactions between other elements and the effects of other elements, even when given in acceptable amounts, on copper status. There should be no constraints in thinking on other possible effects of impaired copper status in humans. I review some of the history of nutritional copper deficiency in infants and children and attempt to interpret some of the clinical manifestations in light of newly acquired information.
Assuntos
Transtornos da Nutrição Infantil/fisiopatologia , Cobre/deficiência , Animais , Transtornos da Nutrição Infantil/tratamento farmacológico , Transtornos da Nutrição Infantil/etiologia , Cobre/fisiologia , Cobre/uso terapêutico , Deficiências Nutricionais/etiologia , Deficiências Nutricionais/fisiopatologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/etiologia , Doenças do Prematuro/fisiopatologiaRESUMO
The inhibitory effect of vanadate species on the enzymatic activity of bovine copper-zinc superoxide dismutase has been investigated at different pH values and vanadium concentrations. A definite inhibitory effect, clearly related to the main negative charge of each of the vanadate solutions, has been found. The results suggest that the origin of the inhibitory effect may be similar to that found for the phosphate ion, i.e., a diminution of the effectiveness of the substrate electronic guidance mechanism by partial neutralization of the charges close to the active site. Under physiological conditions, the inhibitory effect of vanadate is somewhat smaller than the phosphate.