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At least 19 records

Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

NASA Discipline Regulatory Physiology↗

Iron and manganese in anaerobic respiration: environmental significance, physiology, and regulation

Dissimilatory iron and/or manganese reduction is known to occur in several organisms, including anaerobic sulfur-reducing organisms such as Geobacter metallireducens or Desulfuromonas acetoxidans, and facultative aerobes such as Shewanella putrefaciens. These bacteria couple both carbon oxidation and growth to the reduction of these metals, and inhibitor and competition experiments suggest that Mn(IV) and Fe(III) are efficient electron acceptors similar to nitrate in redox abilities and capable of out-competing electron acceptors of lower potential, such as sulfate (sulfate reduction) or CO2 (methanogenesis). Field studies of iron and/or manganese reduction suggest that organisms with such metabolic abilities play important roles in coupling the oxidation of organic carbon to metal reduction under anaerobic conditions. Because both iron and manganese oxides are solids or colloids, they tend to settle downward in aquatic environments, providing a physical mechanism for the movement of oxidizing potential into anoxic zones. The resulting biogeochemical metal cycles have a strong impact on many other elements including carbon, sulfur, phosphorous, and trace metals.

Review, Academic↗

Potential utility of the thematic mapper for surface mine monitoring

One of many potential applications of the thematic mapper (TM) is surface mine monitoring. To assess this potential, data acquired by an aircraft multispectral scanner over Pennsylvania surface mines were preprocessed to simulate the anticipated spectral, spatial, and radiometric characteristics of TM data. False color imagery and thematic maps were derived from the simulated data and compared to imagery and maps derived from LANDSAT multispectral scanner subsystems data. On the basis of this comparison, TM data should definitely increase the detail and accuracy of remotely acquired surface mine information and may enable the remote determination of compliance with reclamation regulations.

Irons, J. R.↗

Oxygen in the Martian atmosphere: Regulation of PO2 by the deposition of iron formations on Mars

During Earth's early history, and prior to the evolution of its present day oxygenated atmosphere, extensive iron rich siliceous sedimentary rocks were deposited, consisting of alternating layers of silica (chert) and iron oxide minerals (hematite and magnetite). The banding in iron formations recorded changes of atmosphere-hydrosphere interactions near sea level in the ancient ocean, which induced the oxidation of dissolved ferrous iron, precipitation of insoluble ferric oxides and silica, and regulation of oxygen in Earth's early atmosphere. Similarities between the Archean Earth and the composition of the present day atmosphere on Mars, together with the pervasive presence of ferric oxides in the Martian regolith suggest that iron formation might also have been deposited on Mars and influenced the oxygen content of the Martian atmosphere. Such a possibility is discussed here with a view to assessing whether the oxygen content of the Martian atmosphere has been regulated by the chemical precipitation of iron formations on Mars.

Burns, Roger G.↗

Photosynthetic characteristics and estimated growth rates indicate grazing is the proximate control of primary production in the equatorial Pacific

Macronutrients persist in the surface layer of the equatorial Pacific because the production of phytoplankton is limited; the nature of this limitation has yet to be resolved. Measurements of photosynthesis as a function of irradiance (P-I) provide information on the control of primary productivity, a question of great biogeochemical importance. Accordingly, P-I was measured in the equatorial Pacific along 150 deg W, during February-March 1988. Diel variability of P-I showed a pattern consistent with nocturnal vertical mixing in the upper 20 m followed by diurnal stratification, causing photoinhibition near the surface at midday. Otherwise, the distribution of photosynthetic parameters with depth and the stability of P-I during simulated in situ incubations over 2 days demonstrated that photoadaptation was nearly complete at the time of sampling: photoadaptation had not been effectively countered by upwelling or vertical mixing. Measurements of P-I and chlorophyll during manipulations of trace elements showed that simple precautions to minimize contamination were sufficient to obtain valid rate measurements and that the specific growth rates of phytoplankton were fairly high in situ, a minimum of 0.6/d. Diel variability of beam attenuation also indicated high specific growth rates of phytoplankton and a strong coupling of production with grazing. It appears that grazing is the proximate control on the standing crop of phytoplankton. Nonetheless, the supply of a trace nutrient such as iron might ultimately regulate productivity by influencing species composition and food-web structure.

Cullen, John J.↗

Microarray analysis identifies Salmonella genes belonging to the low-shear modeled microgravity regulon

The low-shear environment of optimized rotation suspension culture allows both eukaryotic and prokaryotic cells to assume physiologically relevant phenotypes that have led to significant advances in fundamental investigations of medical and biological importance. This culture environment has also been used to model microgravity for ground-based studies regarding the impact of space flight on eukaryotic and prokaryotic physiology. We have previously demonstrated that low-shear modeled microgravity (LSMMG) under optimized rotation suspension culture is a novel environmental signal that regulates the virulence, stress resistance, and protein expression levels of Salmonella enterica serovar Typhimurium. However, the mechanisms used by the cells of any species, including Salmonella, to sense and respond to LSMMG and identities of the genes involved are unknown. In this study, we used DNA microarrays to elucidate the global transcriptional response of Salmonella to LSMMG. When compared with identical growth conditions under normal gravity (1 x g), LSMMG differentially regulated the expression of 163 genes distributed throughout the chromosome, representing functionally diverse groups including transcriptional regulators, virulence factors, lipopolysaccharide biosynthetic enzymes, iron-utilization enzymes, and proteins of unknown function. Many of the LSMMG-regulated genes were organized in clusters or operons. The microarray results were further validated by RT-PCR and phenotypic analyses, and they indicate that the ferric uptake regulator is involved in the LSMMG response. The results provide important insight about the Salmonella LSMMG response and could provide clues for the functioning of known Salmonella virulence systems or the identification of uncharacterized bacterial virulence strategies.

Non-NASA Center↗

Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the short-term consequences of the independent and combined effects of gamma radiation and elevated body iron stores on measures of cardiac structure. We hypothesize that modifications to cardiac structure and function will be greater in rats with high body iron stores and exposed to gamma radiation than in rats that have only 1 of those treatments. Cardiac Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with cardiac structure and function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with cardiac contractile function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment.

Westby, Christian M.↗

Nutritional Biochemistry of Space Flight

Adequate nutrition is critical for maintenance of crew health during and after extended-duration space flight. The impact of weightlessness on human physiology is profound, with effects on many systems related to nutrition, including bone, muscle, hematology, fluid and electrolyte regulation. Additionally, we have much to learn regarding the impact of weightlessness on absorption, m~tabolism , and excretion of nutrients, and this will ultimately determine the nutrient requirements for extended-duration space flight. Existing nutritional requirements for extended-duration space flight have been formulated based on limited flight research, and extrapolation from ground-based research. NASA's Nutritional Biochemistry Laboratory is charged with defining the nutritional requirements for space flight. This is accomplished through both operational and research projects. A nutritional status assessment program is included operationally for all International Space Station astronauts. This medical requirement includes biochemical and dietary assessments, and is completed before, during, and after the missions. This program will provide information about crew health and nutritional status, and will also provide assessments of countermeasure efficacy. Ongoing research projects include studies of calcium and bone metabolism, and iron absorption and metabolism. The calcium studies include measurements of endocrine regulation of calcium homeostasis, biochemical marker~ of bone metabolism, and tracer kinetic studies of calcium movement in the body. These calcium kinetic studies allow for estimation of intestinal absorption, urinary excretion, and perhaps most importantly - deposition and resorption of calcium from bone. The Calcium Kinetics experiment is currently being prepared for flight on the Space Shuttle in 2001, and potentially for subsequent Shuttle and International Space Station missions. The iron study is intended to assess whether iron absorption is down-regulated dUl1ng space flight. This is critical due to the red blood cell changes which occur, and the increase in iron storage that has been observed after space flight. The Iron Absorption and Metabolism experiment is currently planned for long-term flights on the International Space Station.

Smith, Scott M.↗

Space manufacturing 1983; Proceedings of the Sixth Conference, Princeton University, Princeton, NJ, May 9-12, 1983

General topics are biomedical and social sciences, space stations and habitats, space manufacturing, international and legal considerations, materials resources and processing, accelerators and asteroids, and space economics. Among the papers presented, consideration is given to the evolution of man as an explorer; whether people, robots, or hybrids should operate a space station; electrophoresis experiments in space; the emerging government regulation of American space entrepeneurs; the extraction and purification of iron-group and precious metals from asteroidal feedstocks; the construction, testing, and design comparison to computer simulation fo the Mass-Driver III; and the international competition in commercial aerospace markets.

Burke, J. D.↗

Biogenic Methane and the Rise of Oxygen

Oxygenic photosynthesis does not make the rise of oxygen inevitable. What is required is that reductant and oxygen be separated and permanently segregated. The usual picture for Earth is that oxygenic photosynthesis split CO2 into carbon and oxygen, with the carbon buried in sediments and the oxygen mostly taken up by oxides of iron and sulfur. The relatively small atmospheric reservoir of O2 is regulated by the carbon burial rate, reaction with volcanic and metamorphic gases, and oxidation of reduced carbon released as old sediments weather. Absent from this picture is a distinction between the Archean and modern times: on average, carbon burial fluxes would have been matched by oxygen losses then as now. Separation of reductant from oxidant is only provisional. No net oxidation of the continents occurs, and so no change of diagenetic, metamorphic, or volcanic gases is expected. Nor would any change in oxidative weathering be expected. Something more than carbon burial is required to make the Archean different. The escape of hydrogen to space permanently separates the reductant from the oxidant. Hydrogen escape is widely believed to have led to the present highly oxidized states of Mars and Venus. Hydrogen escape has usually been thought small for Archaean Earth, because water vapor is cold-trapped at the troposphere and thus held to levels of a few ppmv in the stratosphere. This cold trapping renders hydrogen escape negligible. However, methane is not cold trapped, and its expected abundance in the Archaean, given low oxygen levels and a biogenic source, would have been high, probably more than 100 times present. At such levels methane would have driven geologically significant levels of hydrogen escape. Additional information is contained in the original extended abstract.

Catling, David↗

Spacecraft transformer and inductor design

The conversion process in spacecraft power electronics requires the use of magnetic components which frequently are the heaviest and bulkiest items in the conversion circuit. This handbook pertains to magnetic material selection, transformer and inductor design tradeoffs, transformer design, iron core dc inductor design, toroidal power core inductor design, window utilization factors, regulation, and temperature rise. Relationships are given which simplify and standardize the design of transformers and the analysis of the circuits in which they are used. The interactions of the various design parameters are also presented in simplified form so that tradeoffs and optimizations may easily be made.

Mclyman, W. T.↗

Murine thymic lymphoma is associated with a species-specific hematopoietic progenitor cell subpopulation

Many strains of laboratory mouse are uniquely susceptible to the development of T cell lymphoma/leukemia, either spontaneously or as a result of chemical or radiation exposure. In contrast, T cell leukemias or lymphomas which are relatively uncommon in human populations, are not easily induced by radiation, and are not generally associated with chemotherapy or chemical exposure. Evidence is presented to suggest that differences in the susceptibility to the development of these malignancies is related to subtle but important variations in the regulation of hematopoietic stem cell differentiation between these two species.

Non-NASA Center↗

Long Life Molten Salt Battery for NASA Venus Application

A development program is being conducted at Advanced Thermal Batteries (ATB) to create a low discharge rate, long life, molten salt battery for a NASA Venus surface probe. Battery goals are 60 days continuous operation at +25V +0/-6 volts and -25V +6/-0 Volts under severe environments of 465°C, 92 atm pressure, and corrosive sulfur dioxide in a super critical carbon dioxide atmosphere. Conveniently, molten salt thermal battery electrochemistry starts to operate efficiently at 330°C. However, a major barrier to direct application of existing thermal battery technology is the high self-discharge rate, resulting in lifetimes in only minutes, not days. The best performance to date, which meets the required voltage regulation, has been a lithium silicon (LiSi) alloy anode discharging through all three voltage plateau versus an iron monosulfide (FeS) cathode. In order to perform reproducibly, additional engineering controls within the battery design are required to limit cell–to–cell parasitic discharge mechanisms. Results of these trials have improved the efficiency and manufacturability of the design.

Thermal Battery↗

Radiation-induced gene expression in the nematode Caenorhabditis elegans

We used the nematode C. elegans to characterize the genotoxic and cytotoxic effects of ionizing radiation in a simple animal model emphasizing the unique effects of charged particle radiation. Here we demonstrate by RT-PCR differential display and whole genome microarray hybridization experiments that gamma rays, accelerated protons and iron ions at the same physical dose lead to unique transcription profiles. 599 of 17871 genes analyzed (3.4%) showed differential expression 3 hrs after exposure to 3 Gy of radiation. 193 were up-regulated, 406 were down-regulated and 90% were affected only by a single species of radiation. A novel statistical clustering technique identified the regulatory relationships between the radiation-modulated genes and showed that genes affected by each radiation species were associated with unique regulatory clusters. This suggests that independent homeostatic mechanisms are activated in response to radiation exposure as a function of track structure or ionization density.

Non-NASA Center↗

p53 deficiency alters the yield and spectrum of radiation-induced lacZ mutants in the brain of transgenic mice

Exposure to heavy particle radiation in the galacto-cosmic environment poses a significant risk in space exploration and the evaluation of radiation-induced genetic damage in tissues, especially in the central nervous system, is an important consideration in long-term manned space missions. We used a plasmid-based transgenic mouse model system, with the pUR288 lacZ transgene integrated in the genome of every cell of C57Bl/6(lacZ) mice, to evaluate the genetic damage induced by iron particle radiation. In order to examine the importance of genetic background on the radiation sensitivity of individuals, we cross-bred p53 wild-type lacZ transgenic mice with p53 nullizygous mice, producing lacZ transgenic mice that were either hemizygous or nullizygous for the p53 tumor suppressor gene. Animals were exposed to an acute dose of 1 Gy of iron particles and the lacZ mutation frequency (MF) in the brain was measured at time intervals from 1 to 16 weeks post-irradiation. Our results suggest that iron particles induced an increase in lacZ MF (2.4-fold increase in p53+/+ mice, 1.3-fold increase in p53+/- mice and 2.1-fold increase in p53-/- mice) and that this induction is both temporally regulated and p53 genotype dependent. Characterization of mutants based on their restriction patterns showed that the majority of the mutants arising spontaneously are derived from point mutations or small deletions in all three genotypes. Radiation induced alterations in the spectrum of deletion mutants and reorganization of the genome, as evidenced by the selection of mutants containing mouse genomic DNA. These observations are unique in that mutations in brain tissue after particle radiation exposure have never before been reported owing to technical limitations in most other mutation assays.

Non-NASA Center↗

Regulation of Blood Volume During Spaceflight

The effects of spaceflight on erythropoiesis and blood volume in the rat were studied during the 14-day NASA Spacelab Life Sciences 2 (SLS-2) Shuttle mission. Measurements included red blood cell mass (RBCM), plasma volume (PV), iron utilization and iron utilization in response to an injection of erythropoietin. Red blood cell (RBC) survival, splenic sequestration and erythrocyte morphology were also evaluated. At landing, the RBCM adjusted for body weight was significantly lower in the flight animals than in the ground controls. While the PV was also decreased, the change was not statistically significant. Incorporation of iron into circulating RBCs was normal when measured after five days of spaceflight and the rat responded normally to the single in-flight injection of erythropoietin. No change in RBC morphology could be attributed to spaceflight. A normal survival was found for the RBC population that was represented by Cr-51 labeled RBCS. These results demonstrate that rats, like humans, return from spaceflight with a decreased RBCM and total blood volume.

Alfrey, Clarence P.↗

Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

NASA Discipline Radiation Health↗

Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency

A role of the copper protein ceruloplasmin (Cp) in iron metabolism is suggested by its ferroxidase activity and by the tissue iron overload in hereditary Cp deficiency patients. In addition, plasma Cp increases markedly in several conditions of anemia, e.g. iron deficiency, hemorrhage, renal failure, sickle cell disease, pregnancy, and inflammation. However, little is known about the cellular and molecular mechanism(s) involved. We have reported that iron chelators increase Cp mRNA expression and protein synthesis in human hepatocarcinoma HepG2 cells. Furthermore, we have shown that the increase in Cp mRNA is due to increased rate of transcription. We here report the results of new studies designed to elucidate the molecular mechanism underlying transcriptional activation of Cp by iron deficiency. The 5'-flanking region of the Cp gene was cloned from a human genomic library. A 4774-base pair segment of the Cp promoter/enhancer driving a luciferase reporter was transfected into HepG2 or Hep3B cells. Iron deficiency or hypoxia increased luciferase activity by 5-10-fold compared with untreated cells. Examination of the sequence showed three pairs of consensus hypoxia-responsive elements (HREs). Deletion and mutation analysis showed that a single HRE was necessary and sufficient for gene activation. The involvement of hypoxia-inducible factor-1 (HIF-1) was shown by gel-shift and supershift experiments that showed HIF-1alpha and HIF-1beta binding to a radiolabeled oligonucleotide containing the Cp promoter HRE. Furthermore, iron deficiency (and hypoxia) did not activate Cp gene expression in Hepa c4 hepatoma cells deficient in HIF-1beta, as shown functionally by the inactivity of a transfected Cp promoter-luciferase construct and by the failure of HIF-1 to bind the Cp HRE in nuclear extracts from these cells. These results are consistent with in vivo findings that iron deficiency increases plasma Cp and provides a molecular mechanism that may help to understand these observations.

NASA Discipline Cardiopulmonary↗