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)

Elevated pCO(2) inhibits cell growth. This growth inhibition is accompanied by a decrease in intracellular pH (pHi), as well as a decrease in glycolysis. Elevated concentrations (mM) of some amino acids have been shown by others to protect cells exposed to two very different environmental stresses: nutrient starvation and hyperosmolality. The fact that many of the amino acids shown to have protective effects against other stresses are transported into the cell through a pHi-sensitive transporter led us to study the possibility of using these amino acids as protective agents under elevated pCO(2). Screening experiments using 5, 15, and 25 mM of each amino acid showed that not all amino acids that protect cells from hyperosmolality protect them from elevated pCO(2). Glycine betaine and glycine were chosen for further characterization in both hybridoma and CHO cells. Asparagine and threonine were also tested in hybridoma and CHO cells, respectively. All amino acids tested under 195 mm Hg pCO(2)/435 mOsm/kg (50% growth inhibition) restored the specific growth rate (mu) in hybridoma cells to that observed under control conditions (40 mm Hg/320 mOsm/kg). Addition of each amino acid resulted in an increase in the consumption rate and intracellular accumulation of that amino acid. In CHO cells, glycine betaine also restored mu to control values, while glycine and threonine partially restored mu. In hybridoma cells, the higher specific antibody productivity obtained at elevated pCO(2) was maintained with the lowest amino acid concentration (5 mM). Productivity decreased toward control values with increasing amino acid concentrations. Elevated pCO(2) decreased the specific tPA productivity in the CHO cell line studied. Only glycine betaine resulted in a 20% increase in productivity at 195 mm Hg/435 mOsm/kg. With the exception of glycine betaine in hybridoma cells, amino acids did not mitigate the associated pHi decrease of at least 0.2 pH units at 195 mm Hg/435 mOsm/kg. pHi in hybridoma cells under elevated pCO(2) in the presence of glycine betaine was about 0.1 pH units below that of control. Amino acids had no effect on the cell size response of hybridoma cells, while they partially offset the increase in CHO cell size at elevated pCO(2). Glycine betaine, asparagine, and glycine increased the specific glucose consumption rate observed at 195 mm Hg/435 mOsm/kg (50% of control) to values greater than 70% of control in hybridoma cells. In CHO cells, only glycine betaine increased q(glc) (by 20%) under elevated pCO(2). All amino acids tested improved the cell yield from glutamine at 195 mm Hg/435 mOsm/kg in both cell lines.
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PMID:Selected amino acids protect hybridoma and CHO cells from elevated carbon dioxide and osmolality. 1200 Nov 66

Two-month-old tomato plants were submitted to day/night cycles and to prolonged darkness in order to investigate the physiological and biochemical response to sugar starvation in sink organs. Roots appeared particularly sensitive to the cessation of photosynthesis, as revealed by the reduction of the growth rate and the decline of the carbohydrate and protein content. Therefore, excised tomato roots were used as a model to deepen the characterization of sugar starvation symptoms. In excised roots, the endogenous sugars were rapidly exhausted and significant degradation of protein was observed. Glutamine and asparagine accounted for most of the nitrogen released by protein breakdown. Respiration declined and proliferation- and growth-associated genes were repressed soon after the beginning of the sugar depletion. Among the genes studied, only the gene encoding asparagine synthetase was strongly induced. All the starvation symptoms were reversible when the roots were resupplied with sugar. When the culture conditions deteriorated, the metabolic and molecular changes led to the triggering of apoptosis of the root cells.
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PMID:Physiological, biochemical and molecular analysis of sugar-starvation responses in tomato roots. 1265 65

The type of dormancy and conditions necessary for germination of Agaricus bisporus basidiospores (BS) were studied. BS failed to germinate on starvation agar and required the presence of carbon and nitrogen (asparagine and/or glucose) sources in the medium. Upon 3-week storage, BS germinated after 4-5 days. Heat shock (20 min at 45 degrees C) and the decreased temperature facilitated activation of germination. Heterocyclic compounds stimulating germination of endogenously dormant spores, such as furfural, failed to activate germination. The data obtained suggested an endogenous dormancy of A. bisporus BS differing from zygospores of Mucorales. BS contained 17-19% lipids with a composition of fatty acids differing from those of pileus and stipe of the fruiting body. The soluble carbohydrates of the cytosol amounted to 12% dry spore weight and consisted of mannitol (74%) and trehalose (26%). Unlike BS stored at 2 degrees C, the BS stored for 5 months at 20 degrees C lost their ability to germinate, which correlated with a decrease in the content of trehalose.
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PMID:[Germination of basidiospores of Agaricus bisporus]. 1512 1

To investigate the effect of l-asparaginase on acute lymphoblastic leukemia (ALL), we used cDNA microarrays to obtain a genome-wide view of gene expression both at baseline and after in vitro exposure to l-asparaginase in cell lines and pediatric ALL samples. In 16 cell lines, a baseline gene expression pattern distinguished l-asparaginase sensitivity from resistance. However, for 28 pediatric ALL samples, no consistent baseline expression pattern was associated with sensitivity to l-asparaginase. In particular, baseline expression of asparagine synthetase (ASNS) was not predictive of response to l-asparaginase. After exposure to l-asparaginase, 5 cell lines and 10 clinical samples exhibited very similar changes in the expression of a large number of genes. However, the gene expression changes occurred more slowly in the clinical samples. These changes included a consistent increase in expression of tRNA synthetases and solute transporters and activating transcription factor and CCAAT/enhancer binding protein family members, a response similar to that observed with amino acid starvation. There was also a consistent decrease in many genes associated with proliferation. Taken together, the changes seem to reflect a consistent coordinated response to asparagine starvation in both cell lines and clinical samples. Importantly, in the clinical samples, increased expression of ASNS after l-asparaginase exposure was not associated with in vitro resistance to l-asparaginase, indicating that ASNS-independent mechanisms of in vitro l-asparaginase resistance are common in ALL. These results suggest that targeting particular genes involved in the response to amino acid starvation in ALL cells may provide a novel way to overcome l-asparaginase resistance.
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PMID:A genome-wide view of the in vitro response to l-asparaginase in acute lymphoblastic leukemia. 1566 6

Many early pregnancy complications are associated with an imbalance in pro- and anti-inflammatory cytokines, resulting in alterations in nitric oxide (NO) profile. Since very little is known about the modus operandi of this free radical in early embryos, this study characterised NO embryotoxicity in terms of bovine embryo development and metabolism. Embryos were generated by in vitro maturation and fertilisation of oocytes aspirated from abattoir-derived ovaries. Zygote to blastocyst rates were measured in SOFaaBSA in the presence and absence of the NO donor sodium nitroprusside (SNP) over the 0-50 microM range (n=10 per group). Since concentrations <10 microM SNP depressed blastocyst rate, blastocyst cell numbers (determined by bisbenzimide staining; n=22 and 20), glucose, pyruvate, lactate (measured ultramicrofluorometrically) and amino acid profiles (quantified by HPLC; n=28 and 23) were assessed at 0 and 10 microM SNP. SNP depressed cell numbers, reduced pyruvate and glucose uptake, perturbed quantitative tyrosine, threonine, phenylalanine, lysine, glycine, tryptophan, methionine and valine profiles, and decreased retention into the negative range (P<0.05). Qualitative asparagine and lysine profiles were affected by SNP, while proportional amino acid production and consumption were increased and decreased, respectively (P<0.05). These findings indicate that SNP (presumably through increases in NO profile): (i) fails to improve bovine embryo development in vitro, (ii) exerts toxic effects, likely through ATP starvation induced by cytochrome c oxidase (oxidative phosphorylation) and glyceraldehyde-3-phosphate dehydrogenase (glycolysis) inhibition, and (iii) may affect albumin endocytosis/hydrolysis or protein biosynthesis, rather than causing a loss of intracellular amino acids or simply depressing their metabolism.
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PMID:Embryotoxicity of the nitric oxide donor sodium nitroprusside in preimplantation bovine embryos in vitro. 1596 59

The role of amino acids in trypanosomatids goes beyond protein synthesis, involving processes such as differentiation, osmoregulation and energy metabolism. The availability of the amino acids involved in those functions depends, among other things, on their transport into the cell. Here we characterize a glutamate transporter from the human protozoan parasite Trypanosoma cruzi. Kinetic data show a single saturable system with a Km of 0.30 mM and a maximum velocity of 98.34 pmoles min(-1) per 2 x 10(7) cells for epimastigotes and 20 pmoles min(-1) per 2 x 10(7) cells for trypomastigotes. Transport was not affected by parasite nutrient starvation for up to 3h. Aspartate, alanine, glutamine, asparagine, methionine, oxaloacetate and alpha-ketoglutarate competed with the substrate in 10-fold excess concentrations. Glutamate uptake was strongly dependent on pH, but not on Na+ or K+ concentrations in the extracellular medium. These data were consistent with the sensitivity of the system to the H+ ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone, suggesting that transport is driven by H+ concentration gradient across the cytoplasmic membrane. The glutamate transport increased linearly with temperature in a range from 15 to 40 degrees C, allowing the calculation of an activation energy of 52.38 kJ/mol.
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PMID:Biochemical characterization of the glutamate transport in Trypanosoma cruzi. 1637 69

In the soil bacterium Pseudomonas fluorescens M114, extracellular proteolytic activity and fluorescent siderophore (pseudobactin M114) production were previously shown to be co-ordinately negatively regulated in response to environmental iron levels. An iron-starvation extracytoplasmic function sigma factor, PbrA, required for the transcription of siderophore biosynthetic genes, was also implicated in M114 protease regulation. The current study centred on the characterization and genetic regulation of the gene(s) responsible for protease production in M114. A serralysin-type metalloprotease gene, aprA, was identified and found to encode the major, if not only, extracellular protease produced by this strain. The expression of aprA and its protein product were found to be subject to complex regulation. Transcription analysis confirmed that PbrA was required for full aprA transcription under low iron conditions, while the ferric uptake regulator, Fur, was implicated in aprA repression under high iron conditions. Interestingly, the iron regulation of AprA was dependent on culture conditions, with PbrA-independent AprA-mediated proteolytic activity observed on skim milk agar supplemented with yeast extract, when supplied with iron or purified pseudobactin M114. These effects were not observed on skim milk agar without yeast extract. PbrA-independent aprA expression was also observed from a truncated transcriptional fusion when grown in sucrose asparagine tryptone broth supplied with iron or purified pseudobactin M114. Thus, experimental evidence suggested that iron mediated its effects via transcriptional activation by PbrA under low iron conditions, while an as-yet-unidentified sigma factor(s) may be required for the PbrA-independent aprA expression and AprA proteolytic activity induced by siderophore and iron.
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PMID:Complex regulation of AprA metalloprotease in Pseudomonas fluorescens M114: evidence for the involvement of iron, the ECF sigma factor, PbrA and pseudobactin M114 siderophore. 1638 13

Chronological life span (CLS) in Saccharomyces cerevisiae, defined as the time cells in a stationary phase culture remain viable, has been proposed as a model for the aging of post-mitotic tissues in mammals. We developed a high-throughput assay to determine CLS for approximately 4800 single-gene deletion strains of yeast, and identified long-lived strains carrying mutations in the conserved TOR pathway. TOR signaling regulates multiple cellular processes in response to nutrients, especially amino acids, raising the possibility that decreased TOR signaling mediates life span extension by calorie restriction. In support of this possibility, removal of either asparagine or glutamate from the media significantly increased stationary phase survival. Pharmacological inhibition of TOR signaling by methionine sulfoximine or rapamycin also increased CLS. Decreased TOR activity also promoted increased accumulation of storage carbohydrates and enhanced stress resistance and nuclear relocalization of the stress-related transcription factor Msn2. We propose that up-regulation of a highly conserved response to starvation-induced stress is important for life span extension by decreased TOR signaling in yeast and higher eukaryotes.
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PMID:Extension of chronological life span in yeast by decreased TOR pathway signaling. 1641 83

Amino acid levels in plants are regulated by a complex interplay of regulatory circuits at the level of enzyme activities and gene expression. Despite the diversity of precursors involved in amino acid biosynthesis as providing the carbon backbones, the amino groups and, for the amino acids methionine and cysteine, the sulfhydryl group and despite the involvement of amino acids as substrates in various downstream metabolic processes, the plant usually manages to provide relatively constant levels of all amino acids. Here we collate data on how amino acid homeostasis is shifted upon depletion of one of the major biosynthetic constituents, i.e., sulfur. Arabidopsis thaliana seedlings exposed to sulfate starvation respond with a set of adaptation processes to achieve a new balance of amino acid metabolism. First, metabolites containing reduced sulfur (cysteine, glutathione, S-adenosylmethionine) are reduced leading to a number of downstream effects. Second, the relative excess accumulation of N over S triggers processes to dump nitrogen in asparagine, glutamine and further N-rich compounds like ureides. Third, the depletion of glutathione affects the redox and stress response system of the glutathione-ascorbate cycle. Thus, biosynthesis of aromatic compounds is triggered to compensate for this loss, leading to an increased flux and accumulation of aromatic amino acids, especially tryptophan. Despite sulfate starvation, the homeostasis is kept, though shifted to a new state. This adaptation process keeps the plant viable even under an adverse nutritional status.
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PMID:Effect of sulfur availability on the integrity of amino acid biosynthesis in plants. 1655 93

The chlorosis symptom that characterizes the halo blight disease of Phaseolus vulgaris L. is caused by phaseolotoxin produced by the plant pathogenic bacterium Pseudomonas syringae pv phaseolicola. Phaseolotoxin is hydrolyzed by plant peptidases to N(delta)(N'-sulpho-diaminophosphinyl) -l-ornithine which also causes chlorosis and is reported to be an irreversible inhibitor of ornithine carbamoyltransferase (OCTase). We have examined the hypothesis that inhibition of OCTase is the primary action of phaseolotoxin that leads to chlorosis.Chlorotic spots appeared on the primary leaves of P. vulgaris seedlings during the 2 days following leaf prick application of a minimum of 30 picomole phaseolotoxin. OCTase in extracts of the lesions was reduced to 20%, or less, of the activity in controls. Four hours after the application of phaseolotoxin the concentration of free ornithine increased more than 2-fold. Other amino acids, especially glutamine and asparagine-but not arginine-increased later. Chlorophyll remained at a constant level in the phaseolotoxin-treated tissue and the appearance of chlorosis was due to the increase in chlorophyll in the surrounding unaffected tissue.Clear halo symptoms developed only on primary leaves of the youngest seedlings (treated 6-7 days after germination). Lesions did not develop on primary leaves of seedlings more than 14 days old, in which the chlorophyll concentration had reached a maximum. OCTase also was inhibited in the symptomless tissue from older leaves treated with phaseolotoxin, but there was no accumulation of amino acids, including ornithine. A single appliction of 200 nanomoles arginine resulted in the complete regreening of the chlorosis caused by phaseolotoxin. Soluble protein was lower in the chlorotic tissue than in the controls, but increased to greater than the control value following the appliction of arginine. These results suggest that phaseolotoxin-induced chlorosis results from reduced chlorophyll synthesis that is associated with arginine-starvation in the tissue where OCTase is inhibited.
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PMID:Association between Symptom Development and Inhibition of Ornithine Carbamoyltransferase in Bean Leaves Treated with Phaseolotoxin. 1666 33


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