Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
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Copper is an essential micronutrient for plants. Present at a high concentration in soil, copper is also regarded as a major toxicant to plant cells due to its potential inhibitory effects against many physiological and biochemical processes. The interference of germination-related proteins by heavy metals has not been well documented at the proteomic level. In the current study, physiological, biochemical and proteomic changes of germinating rice seeds were investigated under copper stress. Germination rate, shoot elongation, plant biomass, and water content were decreased, whereas accumulation of copper and TBARS content in seeds were increased significantly with increasing copper concentrations from 0.2mM to 1.5mM followed by germination. The SDS-PAGE showed the preliminary changes in the polypeptides patterns under copper stress. Protein profiles analyzed by two-dimensional electrophoresis (2-DE) revealed that 25 protein spots were differentially expressed in copper-treated samples. Among them, 18 protein spots were up-regulated and 7 protein spots were down-regulated. These differentially displayed proteins were identified by MALDI-TOF mass spectrometry. The up-regulation of some antioxidant and stress-related proteins such as glyoxalase I, peroxiredoxin, aldose reductase, and some regulatory proteins such as DnaK-type molecular chaperone, UlpI protease, and receptor-like kinase clearly indicated that excess copper generates oxidative stress that might be disruptive to other important metabolic processes. Moreover, down-regulation of key metabolic enzymes like alpha-amylase or enolase revealed that the inhibition of seed germinations after exposure to excess copper not only affects starvation in water uptake by seeds but also results in failure in the reserve mobilization processes. These results indicate a good correlation between the physiological and biochemical changes in germinating rice seeds exposed to excess copper.
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PMID:Excess copper induced physiological and proteomic changes in germinating rice seeds. 1718 80

Trichoderma is widely used as biocontrol agent against phytopathogenic fungi, and as biofertilizer because of its ability to establish mycorriza-like association with plants. The key factor to the ecological success of this genus is the combination of very active mycoparasitic mechanisms plus effective defense strategies induced in plants. This work, different from most of the studies carried out that address the attacking mechanisms, focuses on elucidating how Trichoderma is able to tolerate hostile conditions. A gene from Trichoderma harzianum CECT 2413, qid74, was strongly expressed during starvation of carbon or nitrogen sources; it encoded a cell wall protein of 74kDa that plays a significant role in mycelium protection. qid74 was originally isolated and characterized, in a previous work, by a differential hybridization approach under simulated mycoparasitism conditions. Heterologous expression of Qid74 in Saccharomyces cerevisiae indicated that the protein, located in the cell wall, interfered with mating and sporulation but not with cell integrity. The qid74 gene was disrupted by homologous recombination and it was overexpressed by isolating transformants selected for the amdS gene that carried several copies of qid74 gene under the control of the pki promoter. Disruptants and transformants showed similar growth rate and viability when they were cultivated in different media, temperatures and osmolarities, or were subjected to different abiotic stress conditions. However, disruptants produced about 70% mass yield under any condition and were substantially more sensitive than the wild type to cell wall degradation by different lytic preparations. Transformants had similar mass yield and were more resistant to lytic enzymes but more sensitive to copper sulfate than the wild type. When experiments of adherence to hydrophobic surfaces were carried out, the disruptants had a reduced capacity to adhere, whereas that capacity in the overproducer transformants was slightly higher than that of the wild type. Results point to a significant role for Qid74 both in cell wall protection and adhesion to hydrophobic surfaces.
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PMID:QID74 Cell wall protein of Trichoderma harzianum is involved in cell protection and adherence to hydrophobic surfaces. 1730 Sep 69

Myxococcus xanthus is a soil bacterium that undergoes a unique life cycle among the prokaryotes upon starvation, which includes the formation of macroscopic structures, the fruiting bodies, and the differentiation of vegetative rods into coccoid myxospores. This peculiarity offers the opportunity to study the copper response in this bacterium in two different stages. In fact, M. xanthus vegetative rods exhibit 15-fold-greater resistance against copper than developing cells. However, cells pre-adapted to this metal reach the same levels of resistance during both stages. Analysis of the M. xanthus genome reveals that many of the genes involved in copper resistance are redundant, three of which encode proteins of the multicopper oxidase family (MCO). Each MCO gene exhibits a different expression profile in response to external copper addition. Promoters of cuoA and cuoB respond to Cu(II) ions during growth and development; however, they show a 10-fold-increased copper sensitivity during development. The promoter of cuoC shows copper-independent induction upon starvation, but it is copper up-regulated during growth. Phenotypic analyses of deletion mutants reveal that CuoB is involved in the primary copper-adaptive response; CuoA and CuoC are necessary for the maintenance of copper tolerance; and CuoC is required for normal development. These roles seem to be carried out through cuprous oxidase activity.
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PMID:Differential expression of the three multicopper oxidases from Myxococcus xanthus. 1748 23

Systemic signalling is indispensable for the coordination of diverse physiological processes during development, defence and nutrient allocation. Indirect evidence suggests that plant small RNAs (smRNAs) could be involved in long-distance information transfer via the vasculature of the plant. Analyses of the smRNA complements of vascular exudates from oilseed rape (Brassica napus) showed that xylem sap is devoid of RNA, whereas phloem sap contained a large number of smRNAs. In addition to 32 annotated microRNAs (miRNAs) from 18 different families that could be identified and approved, a set of unknown smRNAs, predominantly of 21 and 24 nucleotides in length, was obtained, and selected candidates were found to be highly abundant in phloem sap. Moreover, we could demonstrate that the levels of three miRNAs known to respond to nutrient deprivation in non-vascular tissue, miR395 (sulphate), miR398 (copper) and miR399 (phosphate), were increased in phloem sap during the growth of plants under the respective starvation conditions. Interestingly, only mature miRNA molecules were found to be stress responsive, demonstrating that single-stranded sense miRNAs are most likely to represent the physiologically relevant molecules. The strong responses in the phloem suggest a role of miRNAs in systemic information transfer via this long-distance transport system.
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PMID:Identification and characterization of small RNAs from the phloem of Brassica napus. 1800 29

The amphipod Melita plumulosa is commonly used to assess the toxicity of contaminated sediments. Seven-day-old M. plumulosa are <1 mm in size, and during 10-day tests in sandy sediments with low nutritional value, starvation can cause >50% mortality. In sediment toxicity tests, therefore, it can be difficult to determine if toxicity is due to contaminants or starvation, particularly in contaminated sandy sediments. This study investigated the influence of amphipod age and food addition on amphipod survival in toxicity tests. The 4-day LC(50) increased linearly from 120 to 470 microg/L when M. plumulosa age at the beginning of the test increased from 5 to 30 days. The addition of food as algae or fish food did not significantly affect the sensitivity of 11-day-old M. plumulosa (11-d Mp) to dissolved copper over 4 days in water-only tests. The survival of 11-d Mp in water-only tests over 10 days was poor without feeding, but when fed fish food, the 10-day LC(50) was 76 +/- 15 microg/L. In sediment tests, feeding 0.063 mg fish food/amphipod on days 3 and 7 of 10-day tests consistently resulted in greater than 80% survival of 11-d Mp for a range of clean, sandy sediments, which had low amphipod survival without added food. Algae were not always suitable as a food source, as their growth can be stimulated by nutrients released from sediment and was inhibited by contaminants. The toxicity of most contaminated sediments was not ameliorated by the addition of food, suggesting that food addition was suitable for inclusion in routine testing protocols for this amphipod.
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PMID:Effect of nutrition on toxicity of contaminants to the epibenthic amphipod Melita plumulosa. 1834 Apr 76

The Cu,Zn superoxide dismutase (Cu,ZnSOD) isolated from Haemophilus ducreyi possesses a His-rich N-terminal metal binding domain, which has been previously proposed to play a copper(II) chaperoning role. To analyze the metal binding ability and selectivity of the histidine-rich domain we have carried out thermodynamic and solution structural analysis of the copper(II) and zinc(II) complexes of a peptide corresponding to the first 11 amino acids of the enzyme (H(2)N-HGDHMHNHDTK-OH, L). This peptide has highly versatile metal binding ability and provides one and three high affinity binding sites for zinc(II) and copper(II), respectively. In equimolar solutions the MHL complexes are dominant in the neutral pH-range with protonated lysine epsilon-amino group. As a consequence of its multidentate nature, L binds zinc and copper with extraordinary high affinity (K(D,Zn)=1.6x10(-9)M and K(D,Cu)=5.0x10(-12)M at pH 7.4) and appears as the strongest zinc(II) and copper(II) chelator between the His-rich peptides so far investigated. These K(D) values support the already proposed role of the N-terminal His-rich region of H. ducreyi Cu,ZnSOD in copper recruitment under metal starvation, and indicate a similar function in the zinc(II) uptake, too. The kinetics of copper(II) transfer from L to the active site of Cu-free N-deleted H. ducreyi Cu,ZnSOD showed significant pH and copper-to-peptide ratio dependence, indicating specific structural requirements during the metal ion transfer to the active site. Interestingly, the complex CuHL has significant superoxide dismutase like activity, which may suggest multifunctional role of the copper(II)-bound N-terminal His-rich domain of H. ducreyi Cu,ZnSOD.
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PMID:Copper and zinc binding properties of the N-terminal histidine-rich sequence of Haemophilus ducreyi Cu,Zn superoxide dismutase. 1856 88

Two decades ago, patients lacking circulating serum ceruloplasmin (Cp) presented with neurodegeneration associated with brain iron accumulation. These patients, with mutations in the MCO (multi-copper oxidase), Cp, revealed an essential role for Cp in iron homoeostasis. The patients were diagnosed in adulthood with CNS (central nervous system) disease and progressed rapidly, making understanding the mechanism of disease imperative. We now know that (i) Cp regulates the efficiency of iron efflux, (ii) Cp stabilizes ferroportin membrane expression, (iii) GPI (glycosylphosphatidylinositol)-linked Cp is the predominant form expressed in brain, (iv) Cp functions as a ferroxidase and regulates the oxidation of Fe(2+) to Fe(3+), (v) Cp does not bind to transferrin directly, and (vi) Cp is one member of a family of mammalian MCOs, which includes hephaestin. It is still unclear how an absence of Cp results in neurodegeneration: is the iron accumulation a primary or secondary injury? Although it is attractive to invoke an iron-mediated oxidative stress mechanism for the neuronal injury and degeneration in aceruloplasminaemia, our data suggest limited redox injury in the brains of mice lacking MCO. In fact, we propose a role for neuronal iron starvation with associated astrocyte and microglial iron overload. With the defect in aceruloplasminaemia being one of inefficient iron efflux from macrophages, we believe that the iron is trapped in a compartment not readily available to participate in oxyradical injury. It is likely that different mechanisms of neuronal cell protection are offered by astrocytes and microglia, and, once these cells are damaged, neuronal survival is compromised.
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PMID:Ceruloplasmin in neurodegenerative diseases. 1902 40

The effect of two different copper conditions (deficiency and excess) on the amino acid composition in B. carinata xylem sap was analysed. When the Cu in the nutrient solution was increased from 0.12 to 2.5 or 5 microM, the concentrations of histidine, threonine, glutamine, proline, methionine, and glycine were much increased in the xylem sap. When Cu was made deficient in the nutrient solution by decreasing its concentration from 0.12 microM to 0 microM, nicotianamine, glutamine, and threonine were significantly increased in the xylem sap. Aqueous solutions containing different Cu-amino acid complexes (simulated saps) responded in a specific way to the changes in pH, providing a signature that was used to evaluate, by comparison with the real xylem sap, the importance of each amino acid in the xylem transport of Cu. For a single amino acid, the free solution Cu(2+) concentration versus pH titration curves for histidine and proline were the most similar to that for xylem under Cu excess. Under Cu deficiency, this Cu concentration versus pH titration curve appeared to be very similar to that for nicotianamine. It is concluded that increased Cu concentrations induced the selective synthesis of certain amino acids in the sap, of which histidine and proline are the most important. Under Cu deficiency, the concentration of nicotianamine was induced the most. The fact that nicotianamine is induced under Cu starvation and not under Cu excess, is in contrast to similar studies indicating species-specific reactions. However, the induction of nicotianamine under Cu starvation is in line with recent molecular data of the role of nicotianamine in intracellular Cu delivery.
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PMID:Nicotianamine and histidine/proline are, respectively, the most important copper chelators in xylem sap of Brassica carinata under conditions of copper deficiency and excess. 1903 52

Organisms from insects to mammals respond to heavy metal load (copper, zinc, cadmium, and mercury) by activating the metal-responsive transcription factor 1 (MTF-1). MTF-1 binds to short DNA sequence motifs, termed metal response elements, and boosts transcription of a number of genes, notably those for metallothioneins. In Drosophila, MTF-1 somewhat counter-intuitively also activates transcription of a copper importer gene (Ctr1B) in response to copper starvation. Here, we report that mutant flies lacking Ctr1B are extremely sensitive to cadmium and mercury treatment, but can be rescued by excess copper in the food. We thus propose that copper, by competing for binding sites on cellular proteins, alleviates the toxic effects of mercury and cadmium. Such a scenario also explains a seemingly fortuitous metal response, namely, that cadmium and mercury strongly induce the expression of a Ctr1B reporter gene. Thus, the transcription enhancer/promoter region of the Ctr1B copper importer gene is subject to three modes of regulation. All of them depend on MTF-1 and all make biological sense, namely, (i) induction by copper starvation, (ii) repression by copper abundance, and (iii), as shown here, induction by cadmium or mercury at normal copper supply.
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PMID:Mercury and cadmium trigger expression of the copper importer Ctr1B, which enables Drosophila to thrive on heavy metal-loaded food. 1904 Mar 55

Nicotianamine (NA) is a non-protein amino acid derivative synthesized from S-adenosyl L-methionine able to bind several metal ions such as iron, copper, manganese, zinc, or nickel. In plants, NA appears to be involved in iron availability and is essential for the plant to complete its biological cycle. In graminaceous plants, NA is also the precursor in the biosynthesis of phytosiderophores. Arabidopsis lines accumulating 4- and 100-fold more NA than wild-type plants were used in order to evaluate the impact of such an NA overaccumulation on iron homeostasis. The expression of iron-regulated genes including the IRT1/FRO2 iron uptake system is highly induced at the transcript level under both iron-sufficient and iron-deficient conditions. Nevertheless, NA overaccumulation does not interfere with the iron uptake mechanisms since the iron levels are similar in the NA-overaccumulating line and wild-type plants in both roots and leaves under both sufficient and deficient conditions. This observation also suggests that the translocation of iron from the root to the shoot is not affected in the NA-overaccumulating line. However, NA overaccumulation triggers an enhanced sensitivity to iron starvation, associated with a decrease in iron availability. This study draws attention to a particular phenotype where NA in excess paradoxically leads to iron deficiency, probably because of an increase of the NA apoplastic pool sequestering iron. This finding strengthens the notion that extracellular NA in the apoplast could be a major checkpoint to control plant iron homeostasis.
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PMID:Increased sensitivity to iron deficiency in Arabidopsis thaliana overaccumulating nicotianamine. 1918 76


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