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PubMed2003

The nature of heme/iron-induced protein tyrosine nitration.

Recently, substantial evidence has emerged that revealed a very close association between the formation of nitrotyrosine and the presence of activated granulocytes containing peroxidases, such as myeloperoxidase. Peroxidases share heme-containing homology and can use H(2)O(2) to oxidize substrates. Heme is a complex of iron with protoporphyrin IX, and the iron-containing structure of heme has been shown to be an oxidant in several model systems where the prooxidant effects of free iron, heme, and hemoproteins may be attributed to the formation of hypervalent states of the heme iron. In the current study, we have tested the hypothesis that free heme and iron play a crucial role in NO(2)-Tyr formation. The data from our study indicate that: (i) hemeiron catalyzes nitration of tyrosine residues by using hydrogen peroxide and nitrite, a reaction that revealed the mechanism underlying the protein nitration by peroxidase, H(2)O(2), and NO(2)(-); (ii) H(2)O(2) plays a key role in the protein oxidation that forms the basis for the protein nitration, whereas nitrite is an essential element that facilitates nitration by the heme(Fe), H(2)O(2), and the NO(2)(-) system; (iii) the formation of a Fe(IV) hypervalent compound may be essential for heme(Fe)-catalyzed nitration, whereas O(2)(*-) (ONOO(-) formation), (*)OH (Fenton reaction), and compound III are unlikely to contribute to the reaction; and (iv) hemoprotein-rich tissues such as cardiac muscle are vulnerable to protein nitration in pathological conditions characterized by the overproduction of H(2)O(2) and NO(2)(-), or nitric oxide.

Animals↗

PubMed2005

Aquisition, mobilization and utilization of cellular iron and heme: endless findings and growing evidence of tight regulation.

Iron is fastidiously utilized by living cells, since it is an essential element, but is toxic in excess. Cells take up iron via a transferrin-transferrin receptor-dependent endocytotic process. The iron thus taken up is used for essential biological functions including oxygen transport, electron transfer, and DNA synthesis. The intracellular level of iron is tightly controlled, through regulation of the cellular uptake of iron and the sequestering of low molecular labile iron into the storage protein ferritin. The known proteins of iron transport and storage, transferrin, transferrin receptor and ferritin, have been recently linked with a number of newly identified proteins that are responsible for inherited diseases of iron metabolisms and play critical roles in the maintenance of iron homeostasis. These proteins are involved in regulation of intracellular levels of iron, iron transport, and heme transport and the oxygen-dependent regulation of gene expression. On the other hand, most iron is transported into mitochondria and immediately used for the biosynthesis of heme in erythroid cells. The heme biosynthesis in mitochondria is coupled with the supply of iron, and the heme, exported from mitochondria, is utilized as prosthetic groups of hemeproteins. Furthermore, non-erythroid and erythroid cells possess the different regulatory systems for the biosynthesis of heme; iron positively regulates the biosynthesis in erythroid cells while heme negatively regulates it in non-erythroid cells. Because of the toxicity and insolubility of heme, the intracellular level of uncommitted heme is maintained at a low concentration (< 10(-9)M). The influx and efflux of heme also help to prevent cytotoxicity. Finally, heme-binding transcriptional factors such as Bach1 and NPAS2 regulate the transcription of several genes involved in the synthesis and degradation of heme-hemeproteins. The discovery of new molecules related to disorders of iron and heme metabolism is ascribable to a complete mechanistic understanding of the cellular network of iron homeostasis. The network of interactions that link iron and heme metabolisms with functions of cellular regulation involving oxidative stress and inflammations contributes to new insights into clinical aspects of disorders.

Animals↗

PubMed2022

Battle for Metals: Regulatory RNAs at the Front Line.

Metal such as iron, zinc, manganese, and nickel are essential elements for bacteria. These nutrients are required in crucial structural and catalytic roles in biological processes, including precursor biosynthesis, DNA replication, transcription, respiration, and oxidative stress responses. While essential, in excess these nutrients can also be toxic. The immune system leverages both of these facets, to limit bacterial proliferation and combat invaders. Metal binding immune proteins reduce the bioavailability of metals at the infection sites starving intruders, while immune cells intoxicate pathogens by providing metals in excess leading to enzyme mismetallation and/or reactive oxygen species generation. In this dynamic metal environment, maintaining metal homeostasis is a critical process that must be precisely coordinated. To achieve this, bacteria utilize diverse metal uptake and efflux systems controlled by metalloregulatory proteins. Recently, small regulatory RNAs (sRNAs) have been revealed to be critical post-transcriptional regulators, working in conjunction with transcription factors to promote rapid adaptation and to fine-tune bacterial adaptation to metal abundance. In this mini review, we discuss the expanding role for sRNAs in iron homeostasis, but also in orchestrating adaptation to the availability of other metals like manganese and nickel. Furthermore, we describe the sRNA-mediated interdependency between metal homeostasis and oxidative stress responses, and how regulatory networks controlled by sRNAs contribute to survival and virulence.

Bacteria↗

PubMed2000

Trace elements and the European skeleton through 5000 years.

For our research, one thousand forty-four samples were taken from the femurs of 522 skeletons from 25 sites in Europe from the Neolithic Age (4000-5000 B.C), from La Téne Period, the Roman Era (500 B.C-400 A.D.), the Middle Ages and from contemporary cadavers. We found the following distribution of elements in the longitudional axis of long bones (the femurs and the tibias). The elements Zn, Fe, Ni, Cr, Pb, Mn, Co and Sn cumulated in the epiphysis. On the other hand, we found that Ca, Sr, Na and K prevailed in the central part of the diaphysis. In the central parts of the cross-section the highest concentration of the metal element Pb was in the external layer from the historical femurs. It was the same with cadavers of the recent population. A specific shift from Neolithic farming to agricultural intensification in the Roman Era was also apparent in the skeletons. Special sources of the above mentioned elements were found both in Celtic and Germanic tribes. Meat is the main source of zinc. Zinc is also important for the growth of the skeleton. When we investigated the development of the human skeleton during the last 5000 years we found the highest concetrations of Zn in communities with a good supply of animal food, whereas the lowest concentrations were paralleled with well-developed agriculturists. We assume the Neolithic gracilization, which is in the background for the increase of agricultural populations, is directly linked with the concentration of Zn and other elements essential for growth (Cu, Fe and others). The individuals most vulnerable to zinc deficiency include infants, adolescents during rapid growth phases and women during pregnancy and lactation. Trace elements in the bones of the La Téne period designate two areas of Celtic diet patterns--a "French one" (Roulier, Mont Trote and Acy Romance) and a "Czech one" (Karlov, Radovesice and Jenisův Ujezd). At Czech sites levels of zinc increased westward towards the Germanic region. Over the Germanic territory in the region of the Saala River there are similar supply trace element sources for bones of the Germanic tribes for a period of more than 1000 years. The dietary customs and environment that formed this development were preserved from 400 B.C. to the period of the Merovingians. A specific ratio of Zn and Sr can be found not only in men, but also in woman and children. At the beginning of our era lead emerged as a civilization element. This element influenced the diet until the 20th century. Since the beginning of the 20th century it occurs much less in the population. On the contrary, we have found significant presence of tin in human bones. Cadavers of the modem population indicate a high content of tin, considerably higher than those in the populations from the beginning of our era (as much as 40 microg.g(-1) bone).

Bone and Bones↗

PubMed1998

Dietary intake of trace elements and polycyclic aromatic hydrocarbons via vegetables grown in an industrial Greek area.

In order to assess the importance of vegetables cultivated in industrialized regions in Greece as a dietary factor, the daily intake of trace elements and PAHs via vegetables were estimated. Intake estimations were based on vegetable availability data and analyses of vegetable contaminants. The mean daily intake of potentially toxic elements ranged between 1.7% (for As) and 23.6% (for Pb) the provisional tolerable daily intakes for adults. Vegetables were found to contribute significantly to the recommended daily intake of essential elements, such as Cr and Mn. The intakes of Cr, Pb, Zn, Co and Hg were highest in spring, whereas the intakes of As and Se were highest in winter. The daily intake of PAHs via vegetables was in general low. The potential doses of carcinogenic PAHs was at the lower range of estimates worldwide.

Adult↗

PubMed1999

The specialist breast care nurse: an evolving role.

The role of the specialist breast care nurse has not previously been described in the Australian context. A study was undertaken, utilising the Delphi technique and focus group interviews to determine the key elements of the role and to describe how these role elements are enacted by the nurses incumbent in these positions in six Australian states. Three rounds of questionnaires to 16 expert nurses established a consensus view as to the essential elements of the specialist breast care nurse's role. The 11 role elements that became significant during analysis of these data were: specialist nurse, supporter, educator, counsellor, adviser, team member, resource person, caregiver, public advocate, manager and researcher. Focus groups were held with nurses from each state and the findings allowed enhancement of the data from the questionnaires. Analysis of the interview data allowed a fuller description of how the nurses actualised their role. This data showed that the specialist breast care nurse co-ordinated the care of the woman and her family during the breast cancer journey. Integral to the role was the support for the woman and her family. It is concluded that in order to perform successfully in the role nurses require specialist education in supportive care, counselling, pathology and treatment of breast cancer, a broad knowledge of oncology nursing, management, research and teaching techniques.

Attitude of Health Personnel↗

PubMed2006

[Determination of metal elements in six kinds of desert plants in Inner Mongolia by ICP-AES].

In the present paper, the contents of metal elements from six kinds of desert plants, namely Haloxylon ammodendron, Caragana microphylla, Ammopiptanthus mongolicus, Salix bordensis, Elaeagnus angusti folia, and Salix psammophila in Inner Mongolian were determined by ICP-AES technique. The recovery ratio obtained by standard addition method ranged between 94.98% and 120.25%, and the RSD was lower than 3.4%. The results of determination showed that the major elements Ca, K, Mg, Na and Al, and trace elements essential to plant vital activities such as Fe, Mn, Cu and Zn exhibit different orders in content in the six kinds of desert plants, and the contents of four elements, Fe, Mn, Cu and Zn are lower than the average content of terrestrial plants. The above results provided reliable data and theory bases for improving environment in west China and choosing weather-resistant and sand-fixation tree species.

China↗

PubMed1999

Concentrations of trace elements in sera of newborns, young infants, and adults.

Concentrations of trace elements in newborns, infants, and adults may be significantly different from each other. Serum trace element reference ranges for different age groups are of value for diagnostic purposes. Inductively coupled plasma-mass spectrometry was applied to the determination of the 21 trace elements Ba, Be, Bi, Ca, Cd, Co, Cs, Cu, La, Li, Hg, Mg, Mn, Mo, Pb, Rb, Sb, Sn, Sr, TI, and Zn in a total of 117 sera of individuals representing different age groups. After microwave-assisted acid digestion with high-purity reagents, 20 umbilical cord sera, 5 sera of fully breast-fed infants, 6 sera of formula-fed infants, 66 sera of patients suffering internal diseases, and 20 sera of healthy blood donors were analyzed for trace elements. One serum and two whole-blood reference materials were analyzed for quality control. Experimental concentrations were in good agreement with certified values. Umbilical cord serum concentrations of the essential elements Ca, Co, Cu, and Mg and of the nonessential and toxic elements Ba, Be, Li, Pb, and Sb were elevated compared to the elemental concentrations in the sera of infants and adults. Serum levels of Ba, Ca, Co, Mn, Pb, and Sb of infants were much higher and serum Cu was significantly lower than in adults. Serum Cu increased significantly with age (newborns: 353 microg/L; infants: 755 microg/L; healthy adults: 810 microg/L), whereas for other trace elements no age-dependence could be established.

Adult↗

PubMed1997

A time to listen.

As methods of health care delivery, and advances in technology change our lives and practices, an essential element of personal and professional relationships has become neglected. We have stopped listening to each other, to our patients, and to ourselves; we have lost the art of communication. The essential aspects of optimal communication and the power of nonverbal signals are reviewed. Only by recognizing the importance of communication in surgical education, practice, and in fact in all aspects of daily life, will this encroaching societal deafness be rebuffed.

Communication↗

PubMed1995

A composite Ets/Pit-1 binding site in the prolactin gene can mediate transcriptional responses to multiple signal transduction pathways.

Binding sites for the tissue-specific transcription factor, Pit-1, are required for basal and hormonally induced prolactin gene transcription. Although Pit-1 is phosphorylated in response to several signaling pathways, the mechanism by which Pit-1 contributes to hormonal induction of gene transcription has not been defined. Recent reports suggest that phosphorylation of Pit-1 may not be required for hormonal regulation of the prolactin promoter. Analysis of the contribution of individual Pit-1 binding sites has been complicated due to the fact that some of the elements appear to be redundant. To better understand the role of Pit-1 sites in mediating hormonal regulation of the prolactin gene, we have performed enhancer tests using the three most proximal Pit-1 binding sites of the rat prolactin gene which are designated the 1P, 2P, and 3P sites. The results demonstrate that multimers of the 3P Pit-1 binding site are much more responsive to several hormonal and intracellular signaling pathways than multimers of the 1P or 2P sites. The 3P DNA element was found to contain a consensus binding site for the Ets family of proteins. Mutation of the Ets binding site greatly decreased the ability of epidermal growth factor, phorbol esters, Ras, or the Raf kinase to induce reporter gene activity. Mutation of the Ets site had little effect on basal enhancer activity. In contrast, mutation of the consensus Pit-1 binding site in the 3P element essentially abolished all basal enhancer activity. Overexpression of Ets-1 in GH3 pituitary cells enhanced both basal and Ras induced activity from the 3P enhancer. These data describe a composite element in the prolactin gene containing binding sites for two different factors and the studies suggest a mechanism by which Ets proteins and Pit-1 functionally cooperate to permit transcriptional regulation by different signaling pathways.

Animals↗

PubMed2006

Chronic kidney disease management--what can we learn from South African and Australian efforts?

BACKGROUND: The prevalence of chronic kidney disease is on the rise. Our objective is to describe two programs to improve the awareness and management of hypertension, renal disease, and diabetes in remote Australian Aboriginal and urban and periurban South African communities. We focus on how the Australian Aboriginal and South African Chronic Disease Outreach Programs have worked together. METHODS: The establishment of prevention programs in developing countries is a challenge. The paper evaluates these challenges, including accessing international aid. The programs advocate that regular integrated checks for chronic disease and their risk factors are essential elements of regular adult health care. Programs should be run by primary health workers, following algorithms for testing and treatment, and a backup provided by nurse coordinators. Constant evaluation is essential to develop community health profiles and adapt program structure. RESULTS: Both programs are discussed, including how they are organized to deliver preventative and treatment strategies. The challenges and adaptations required are outlined. CONCLUSIONS: It is the aim of the international kidney community to prevent chronic kidney disease. The South African and Australian groups highlight the need for a systematic and sustained approach to the management of chronic diseases to achieve this goal.

Australia↗

PubMed1986

Nutrition, immune response, and outcome.

The immune system plays a key role in the body's ability to fight infection and reduce the risk of developing tumors, autoimmune and degenerative disease. Nutritional deficiencies and excesses influence various components of the immune system. Early studies investigating the association between nutrition and immunity focused on generalized protein-energy malnutrition, particularly in children in developing countries. The extent of immunological impairment depends not only on the severity of malnutrition but on the presence of infection and on the age of onset of nutritional deprivation, among other factors. In industrialized nations, immune function has been shown to be compromised in many malnourished hospitalized patients, small-for-gestational age infants, and the elderly. Obesity also may adversely influence immune function. Imbalances of single nutrients are relatively uncommon in humans, and investigations of protein and amino acids and specific vitamins, minerals, and trace elements generally are carried out in experimental animals. Deficiencies of protein and some amino acids, as well as vitamins A, E, B6 and folate, are associated with reduced immunocompetence. In contrast, excessive intake of fat, in particular polyunsaturated fatty acids (e.g. linoleic and arachidonic acids), iron, and vitamin E are immunosuppressive. Trace elements modulate immune responses through their critical role in enzyme activity. Both deficiency and excess of trace elements have been recognized. Although dietary requirements of most of these elements are met by a balanced diet, there are certain population groups and specific disease states which are likely to be associated with deficiency of one or more of these essential elements. The role of trace elements in maintenance of immune function and their causal role in secondary immunodeficiency is increasingly being recognized. There is growing research concerning the role of zinc, copper, selenium, and other elements in immunity and the mechanisms that underlie such roles. The problem of interaction of trace elements and immunity is a complex one because of the frequently associated other nutritional deficiencies, the presence of clinical or subclinical infections which in themselves have a significant effect on immunity, and finally the altered metabolism due to the underlying disease. There are many practical applications of our recently acquired knowledge regarding nutritional regulation of immunity.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

PubMed1998

Modulation of cell calcium signals by mitochondria.

It is now clearer and clearer that mitochondria play a role, and perhaps an active role, in cell calcium signalling. The fact that mitochondria can exhibit a Ca2+-induced Ca2+ release (mCICR, Ichas et al. [37]) reinforces this concept and makes the mitochondria an essential element in the relay of Ca2+ wave propagation. It must be emphasized that the modulation of cell Ca2+ signals by mitochondria depends upon their energetic status, thus making mitochondria an essential link between energy metabolism and calcium signalling inside the cell.

Adenine Nucleotides↗

PubMed1986

Mutational analysis of DNA sequences affecting the replication of defective polyomavirus variant D-50.

The genome of the defective polyomavirus variant D-50 consists of tandemly repeated DNA segments. The repeat unit corresponds to a 17% fragment of polyomavirus DNA (Griffin and Fried (1975) Nature 256, pp. 175-179). To allow mutational analysis, a monomer unit of D-50 DNA was cloned. After excision from the plasmid and ligation to form a random mixture of products, circular head to tail oligomers of the cloned segment were replicated in transfected cells. Those molecules had the same replication properties as original D-50 DNA. Deletion of base sequences assumed to be at the origin of DNA synthesis inhibited the replication completely, whereas a deletion of a segment at the junction of the tandem repeats had only a slight inhibitory effect. Mutation of potential coding sequences of the variant genome had a slight stimulatory effect on DNA synthesis, ruling out that D-50 expresses any protein that stimulates replication. In an attempt to construct variants similar to D-50, cells were transfected with polyomavirus DNA fragments including the sequences of the D-50 monomer unit. However, all these molecules replicated very slowly, suggesting the presence of an element that inhibited DNA synthesis. The combined data show that D-50 genomes can be reconstituted by ligation of monomer units and that the origin of DNA replication was the only essential element of the variant genome, whereas other elements had cis-acting auxiliary functions.

Base Sequence↗

PubMed1993

Recognition of tRNA(Cys) by Escherichia coli cysteinyl-tRNA synthetase.

A study of the recognition of tRNA(Cys) by Escherichia coli cysteinyl-tRNA synthetase using in vivo and in vitro methods was performed. All three anticodon nucleotides, the discriminator nucleotide (73), and some elements within the tertiary domain (the D stem/loop, the T psi C stem/loop, and the variable loop) are important for recognition; the anticodon stem and acceptor stem appear to contain no essential elements. A T7 RNA polymerase transcript corresponding to tRNA(Cys) is only a 5.5-fold worse substrate than native tRNA(Cys) (in terms of the specificity constant, kcat/Km), mainly due to an increase in the value of Km for the transcript. The greatest loss of specificity caused by mutation of a single nucleotide occurs when the discriminator U73 is changed; kcat/Km declines 3-4 orders of magnitude depending on the substitution. Mutations in the wobble nucleotide of the anticodon also cause reductions in the specificity constant of 3 orders of magnitude, while mutations in the other anticodon nucleotides caused lesser effects. Interestingly, a C35A mutation (with the phenylalanine anticodon GAA) had no effect on aminoacylation by the cysteinyl-tRNA synthetase. Several amber suppressor tRNAs were constructed whose in vivo identity did not correlate with their in vitro specificity, indicating the need for both types of experiments to understand the factors which maintain tRNA specificity.

Acylation↗

PubMed2004

Dynamic model for the accumulation of cadmium and zinc from water and sediment by the aquatic oligochaete, Tubifex tubifex.

In aquatic environments, organisms are exposed to and accumulate metals via waterborne and dietary routes including ingested sediment. A key element in understanding metal uptake and accumulation is information concerning the relative importance of the routes of uptake and the kinetics of the processes. In this work the bioaccumulation of the essential element zinc and the nonessential element cadmium were studied from the aqueous and sediment phase, in the cosmopolitan oligochaete Tubifex tubifex, using the radiotracers 109Cd and 65Zn. A compartmental kinetic model was constructed and parametrized by fitting the model to metal body concentrations. Using the pharmacokinetic modeling approach and taking into account the distribution of the metal between water and sediment, the different routes were quantitatively separated. Under the experimental conditions, the sediment phase accounted for 9.8% of the cadmium and 52% of the zinc uptake. These values are based on the uptake of the radiotracers spiked sediments and therefore likely represent maximal values since it was shown that under the specific conditions this was the most mobile metal fraction. This difference was largely explained by the large difference in assimilation efficiency between cadmium and zinc. Simulations of different conditions showed that both dissolved and sediment-associated metal can be important sources of metal exposure for the worms and that the relative importance strongly depends on the metal and exposure conditions including the lability of the metals in the sediment phase.

Animals↗

PubMed1992

The LIM family transcription factor Isl-1 requires cAMP response element binding protein to promote somatostatin expression in pancreatic islet cells.

Many eukaryotic genes are regulated by cAMP through a conserved cAMP response element (CRE). Here we show that, in the pancreatic islet cell line Tu6, a well-characterized CRE in the somatostatin gene does not provide cAMP responsiveness but functions as an essential element for its basal activity. DNA-binding and functional analyses indicate that the cAMP-responsive factor CREB regulates somatostatin expression in these cells without requirement for phosphorylation at the protein kinase A-regulated Ser-133 phosphorylation site. In addition to the CRE site, cell-specific expression of the somatostatin gene requires a second promoter element, which binds the recently characterized LIM family protein Isl-1. Thus, Isl-1 and CREB appear to synergize on the somatostatin promoter to stimulate high-level expression in Tu6 cells. The ability of CREB to function in a phosphorylation-independent manner suggests a mechanism by which this protein can regulate gene transcription.

Base Sequence↗

PubMed1993

A short 5'-flanking region mediates glucose repression of amylase gene expression in Drosophila melanogaster.

Expression of the alpha-amylase gene is highly repressed by dietary glucose in Drosophila melanogaster larvae. Here, we show that glucose repression is controlled by DNA sequences that are located upstream of the transcribed region. Recombinant gene constructions, in which the amylase promoter sequences were fused with the transcribed region of the Adh gene, were expressed in transgenic Drosophila larvae. The expression of ADH from the recombinant gene was shown to be subject to glucose repression. The function of potential regulatory cis-acting elements within the glucose responsive upstream region was examined by deletion analysis and by site-directed mutagenesis, coupled with expression assays in transformed larvae. The upstream deletion analysis showed that essential elements, both for overall activity and for glucose repression of the amylase gene, are located within a 109-bp region upstream of the transcription start site. Site-directed mutagenesis of these upstream sequences showed that the TATA motif, at position -31, and a novel 36-bp element, at position -109, were necessary for full activity of the amylase promoter. None of the introduced mutations resulted in loss of glucose responsiveness. These results indicate that glucose repression, in Drosophila, is mediated by transcriptional mechanisms that involve multiple, functionally redundant DNA elements.

Animals↗