Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zinc is essential for cell proliferation, differentiation, and viability. When zinc becomes limited for cultured cells, DNA synthesis ceases and the cell cycle is arrested. The molecular mechanisms of actions of zinc are believed to involve changes in the availability of zinc(II) ions (Zn(2+)). By employing a fluorescent Zn(2+) probe, FluoZin-3 acetoxymethyl ester, intracellular Zn(2+) concentrations were measured in undifferentiated and in nerve growth factor (NGF)-differentiated rat pheochromocytoma (PC12) cells. Intracellular Zn(2+) concentrations are pico- to nanomolar in PC12 cells and are higher in the differentiated than in the undifferentiated cells. When following cellular Zn(2+) concentrations for 48 h after the removal of serum, a condition that is known to cause cell cycle arrest, Zn(2+) concentrations decrease after 30 min but, remarkably, increase after 1 h, and then decrease again to about one half of the initial concentration. Cell proliferation, measured by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, decreases after both serum starvation and zinc chelation. Two peaks of Zn(2+) concentrations occur within one cell cycle: one early in the G1 phase and the other in the late G1/S phase. Thus, fluctuations of intracellular Zn(2+) concentrations and established modulation of phosphorylation signaling, via an inhibition of protein tyrosine phosphatases at commensurately low Zn(2+) concentrations, suggest a role for Zn(2+) in the control of the cell cycle. Interventions targeted at these picomolar Zn(2+) fluctuations may be a way of controlling cell growth in hyperplasia, neoplasia, and diseases associated with aberrant differentiation.
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PMID:Transient fluctuations of intracellular zinc ions in cell proliferation. 1946 29

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium that is the causative agent of common sexually transmitted diseases and the leading cause of preventable blindness worldwide. It has been observed that YtgA (CT067) is very immunogenic in patients with chlamydial genital infections. Homology analyses suggested that YtgA is a soluble periplasmic protein and a component of an ATP-binding cassette (ABC) transport system for metals such as iron. Since little is known about iron transport in C. trachomatis, biochemical assays were used to determine the potential role of YtgA in iron acquisition. (59)Fe binding and competition studies revealed that YtgA preferentially binds iron over nickel, zinc or manganese. Western blot and densitometry techniques showed that YtgA concentrations specifically increased 3-5-fold in C. trachomatis, when cultured under iron-starvation conditions rather than under general stress conditions, such as exposure to penicillin. Finally, immuno-transmission electron microscopy provided evidence that YtgA is more concentrated in C. trachomatis during iron restriction, supporting a possible role for YtgA as a component of an ABC transporter.
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PMID:Chlamydia trachomatis YtgA is an iron-binding periplasmic protein induced by iron restriction. 1955 90

Maintaining intracellular zinc levels is critical, because zinc serves as a cofactor for many required enzymes and is toxic in excess. Bacillus subtilis Zur, a Fur family repressor, controls the zinc starvation response including two ribosomal proteins (r-proteins) paralogous to L31 and S14. Biochemical analyses suggest that Zur-controlled r-proteins (which lack the two CXXC metal-binding motifs) may functionally replace their cognate zinc-requiring proteins during zinc limitation. We demonstrate here that Zur regulates the expression of an additional r-protein paralog, RpmGC (L33c), and, using strains defective in zinc uptake, we investigate the physiological contributions of all three Zur-regulated r-proteins. In the 168 lineage, rpmGC is a pseudogene containing a frameshift mutation. Correction of this mutation allows expression of a functional L33c that can suppress the poor growth phenotype of an rpmGA rpmGB (encoding L33a, L33b) double mutant. Similarly, we provide physiological evidence in support of the "failsafe" model (Y. Natori et al., Mol. Microbiol. 63:294-307, 2007) in which the Zur-regulated S14 paralog YhzA allows continued ribosome synthesis when there is insufficient zinc to support S14 function. The L31 paralog YtiA can replace L31 and complement the growth defect of an rpmE mutant (Nanamiya et al., Mol. Microbiol. 52:273-283). We show that, under zinc starvation conditions, derepression of YtiA significantly increases the growth of cells in which preexisting ribosomes carry, as the sole L31 protein, RpmE (containing zinc), but not if they carry YtiA (which lacks zinc). These results support a direct and physiologically relevant role for YtiA in mobilizing zinc from ribosomes.
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PMID:Contributions of Zur-controlled ribosomal proteins to growth under zinc starvation conditions. 1964 45

Selenium-Binding Protein1 (SBP1) gene expression was studied in Arabidopsis (Arabidopsis thaliana) seedlings challenged with several stresses, including cadmium (Cd), selenium {selenate [Se(VI)] and selenite [Se(IV)]}, copper (Cu), zinc (Zn), and hydrogen peroxide (H(2)O(2)) using transgenic lines expressing the luciferase (LUC) reporter gene under the control of the SBP1 promoter. In roots and shoots of SBP1LUC lines, LUC activity increased in response to Cd, Se(VI), Cu, and H(2)O(2) but not in response to Se(IV) or Zn. The pattern of expression of SBP1 was similar to that of PRH43, which encodes the 5'-Adenylylphosphosulfate Reductase2, a marker for the induction of the sulfur assimilation pathway, suggesting that an enhanced sulfur demand triggers SBP1 up-regulation. Correlated to these results, SBP1 promoter showed enhanced activity in response to sulfur starvation. The sulfur starvation induction of SBP1 was abolished by feeding the plants with glutathione (GSH) and was enhanced when seedlings were treated simultaneously with buthionine sulfoxide, which inhibits GSH synthesis, indicating that GSH level participates in the regulation of SBP1 expression. Changes in total GSH level were observed in seedlings challenged with Cd, Se(VI), and H(2)O(2). Accordingly, cad2-1 seedlings, affected in GSH synthesis, were more sensitive than wild-type plants to these three stresses. Moreover, wild-type and cad2-1 seedlings overexpressing SBP1 showed a significant enhanced tolerance to Se(VI) and H(2)O(2) in addition to the previously described resistance to Cd, highlighting that SBP1 expression decreases sensitivity to stress requiring GSH for tolerance. These results are discussed with regard to the potential regulation and function of SBP1 in plants.
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PMID:Arabidopsis putative selenium-binding protein1 expression is tightly linked to cellular sulfur demand and can reduce sensitivity to stresses requiring glutathione for tolerance. 1971 Feb 30

Anoxic and metabolic stresses in large-scale cell culture during biopharmaceutical production can induce apoptosis. Strategies designed to ameliorate the problem of apoptosis in cell culture have focused on mRNA knockdown of pro-apoptotic proteins and over-expression of anti-apoptotic ones. Apoptosis in cell culture involves mitochondrial permeabilization by the pro-apoptotic Bak and Bax proteins; activity of either protein is sufficient to permit apoptosis. We demonstrate here the complete and permanent elimination of both the Bak and Bax proteins in combination in Chinese hamster ovary (CHO) cells using zinc-finger nuclease-mediated gene disruption. Zinc-finger nuclease cleavage of BAX and BAK followed by inaccurate DNA repair resulted in knockout of both genes. Cells lacking Bax and Bak grow normally but fail to activate caspases in response to apoptotic stimuli. When grown using scale-down systems under conditions that mimic growth in large-scale bioreactors they are significantly more resistant to apoptosis induced by starvation, staurosporine, and sodium butyrate. When grown under starvation conditions, BAX- and BAK-deleted cells produce two- to fivefold more IgG than wild-type CHO cells. Under normal growth conditions in suspension culture in shake flasks, double-knockout cultures achieve equal or higher cell densities than unmodified wild-type cultures and reach viable cell densities relevant for large-scale industrial protein production.
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PMID:BAK and BAX deletion using zinc-finger nucleases yields apoptosis-resistant CHO cells. 1977 80

The current economic crisis and food price increase may have a widespread impact on the nutritional and health status of populations, especially in the developing world. Gains in child survival over the past few decades are likely to be threatened and millennium development goals will be harder to achieve. Beyond starvation, which is one of the causes of death in famine situations, there are numerous nutritional pathways by which childhood mortality can increase. These include increases in childhood wasting and stunting, intrauterine growth restriction, and micronutrient deficiencies such as that of vitamin A, iron, and zinc when faced with a food crisis and decreased food availability. These pathways are elucidated and described. Although estimates of the impact of the current crisis on child mortality are yet to be made, data from previous economic crises provide evidence of an increase in childhood mortality that we review. The current situation also emphasizes that there are vast segments of the world's population living in a situation of chronic food insecurity that are likely to be disproportionately affected by an economic crisis. Nutritional and health surveillance data are urgently needed in such populations to monitor both the impacts of a crisis and of interventions. Addressing the nutritional needs of children and women in response to the present crisis is urgent. But, ensuring that vulnerable populations are also targeted with known nutritional interventions at all times is likely to have a substantial impact on child mortality.
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PMID:Impact of the economic crisis and increase in food prices on child mortality: exploring nutritional pathways. 1992 84

NO one has so far produced anything approaching a clear picture of either fat or carbohydrate metabolism and the interactions of the two are still more involved and elusive although they clearly exist. Plants and animals build up reserves of fat from carbohydrate, but the reverse process (fat into carbohydrate), proved in plant seeds, is still unproven in animals, although theoretically possible.In normal human metabolism fat-carbohydrate interactions are almost hidden. The disturbances shown in the metabolism of a diabetic seem to give us the clearest indications of these interactions. Either carbohydrate or fat can be used as the main source of body fuel, but their metabolic course is very different, both as regards chemistry and function. It is only whep carbohydrate is not available, either in starvation or severe diabetes, that fat provides the fuel of the body; this contrast is also manifest in the blood and internal organs, especially the liver. Under the commonest normal conditions of diet carbohydrate is predominantly and preferentially used for metabolism. The liver is rich in glycogen, poor in fat; the blood fat is minimal and ketone bodies, although perhaps present in small amount in the blood at most times, are absent on common tests. As soon as carbohydrate is insufficiently available for the needs of metabolism, depot fat flows to the liver and is there catabolized to ketone bodies which recent proof has shown to be burned peripherally in the muscles independent of carbohydrate metabolism. This is a normal process, harmful only in diabetes, and especially harmful when it occurs suddenly, e.g. when insulin is cut off from a fat diabetic dog or human patient. A diabetic supports with ease a prolonged severe ketosis but suffers from one of sudden onset, although of milder severity. Insulin in the diabetic and sugar in the starved switches metabolism from fat to carbohydrate usage very quickly and ketonuria usually disappears in three to six hours."Diabetic obesity" is very common and is often seen in the earliest stages and again after insulin treatment. It seems probable that hyperglycaemia causes this obesity and this has been clearly established by observations on an unusual case of lipaemia, diabetes and lipodystrophy.Lipaecmia may occur in two opposite phases of metabolism, one anabolic-when fat is on its way to storage, the other catabolic-when it is flowing from stores to the liver. The latter is the usual condition obvious in disease.Work has also been done which suggests that other lipotropic factors-choline, lipocaic, &c., exert an influence on carbohydrate-fat balance, more specifically the glycogen-fat balance in the liver.In America attention has been drawn to the frequent and persistenzt occurrence of fatty enlargement of the liver in diabetic children. The author has seen many diabetic children (usually in a state of chronic ketosis) with enlarged livers, but such enlargement has rapidly disappeared with better management of the diabetes. Only two out of some 500 diabetic children have clearly shown the unmistakable syndrome of "hepatomegalic dwarfism ". In these two cases choline and lipocaic were given over prolonged periods without any effect: the liver, however, of one of these cases has since become normal by the addition of zinc protamine insulin.
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PMID:Interactions of Fat and Carbohydrate Metabolism-New Aspects and Therapies: (Section of Therapeutics and Pharmacology). 1999 15

Inorganic phosphate (Pi) is an essential nutrient for plants, and the low bioavailability of Pi in soils is often a limitation to growth and development. Consequently, plants have evolved a range of regulatory mechanisms to adapt to phosphorus-starvation in order to optimise uptake and assimilation of Pi. Recently, significant progress has been made in elucidating these mechanisms. The coordinated expression of a large number of genes is important for many of these adaptations. Several global expression studies using microarray analysis have been conducted in Arabidopsis thaliana. These studies provide a valuable basis for the identification of new regulatory genes and promoter elements to further the understanding of Pi-dependent gene regulation. With focus on the Arabidopsis transcriptome, we extract common findings that point to new groups of putative regulators, including the NAC, MYB, ethylene response factor/APETALA2, zinc-finger, WRKY and CCAAT-binding families. With a number of new discoveries of regulatory elements, a complex regulatory network is emerging. Some regulatory elements, e.g. the transcription factor PHR1 and the microRNA (miRNA) miR399 and associated factors are well documented, yet not fully understood, whereas other suggested components need further characterisation. Here, we evaluate the contribution of the regulatory elements to the P-responses and present a model comprising factors directly or indirectly involved in transcriptional regulation and the role of miRNAs as regulators and long-distance signals. A striking feature is a series of feedback loops and parallel mechanisms that can modify and attenuate responses. We suggest that these mechanisms are instrumental in providing an accurate response and in keeping P-homeostasis.
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PMID:Dissecting the plant transcriptome and the regulatory responses to phosphate deprivation. 2011 36

Iron (Fe) deficiency is counteracted by a suite of responses to ensure maintenance of vital processes for which Fe is essential. Here, we report on transcriptional changes upon Fe deficiency, investigated in two Arabidopsis (Arabidopsis thaliana) accessions, Columbia (Col-0) and C24. Functional modules of the Arabidopsis Fe deficiency syndrome were inferred from clustering of Fe-responsive genes according to their coexpression. It was found that the redistribution of transition metals is an integral part of the reduction-based response to Fe starvation. The differential expression of metal transporters under the control of the FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR appeared to reflect an anticipated reaction rather than a response to the actual change in metal distribution. In contrast, the regulation of the zinc transporters ZRT/IRT-LIKE PROTEIN2 (ZIP2), ZIP3, ZIP4, and ZIP9 was dependent on the cellular zinc level, and their regulation by Fe was a secondary effect. Cellular Fe homeostasis was found to be closely coupled to Fe-related processes in the plastids. Using clustered genes as bait in gene-fishing experiments, we were able to attribute potentially important roles for gene candidates that have no previously described function in the Fe deficiency response. These results demonstrate a conceptually novel and integrative view into the regulation and interactions that allow Arabidopsis to adapt to suboptimal Fe availability.
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PMID:Transcriptional profiling of the Arabidopsis iron deficiency response reveals conserved transition metal homeostasis networks. 2018 52

Zinc pyrithione has been used in anti-dandruff shampoos and in anti-fouling paint on ships. However, little is known of its mode of action. We characterized the effects of sub-lethal concentrations of zinc pyrithione (Zpt) on Saccharomyces cerevisiae using DNA microarrays. The majority of the strongly upregulated genes are related to iron transport, and many of the strongly downregulated genes are related to the biosynthesis of cytochrome (heme). These data suggest that Zpt induces severe iron starvation. To confirm the DNA microarray data, we supplemented cultures containing Zpt with iron, and the growth of the yeast was restored significantly. From these results, we propose that the principal toxicity of zinc pyrithione arises from iron starvation.
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PMID:DNA microarray analysis suggests that zinc pyrithione causes iron starvation to the yeast Saccharomyces cerevisiae. 2034 71


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