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)

Methyl phosphonate at concentrations up to 20 mM was found to be non toxic towards the growth of Dictyostelium amoebae and the starvation-induced differentiation program. In contrast, phenyl phosphonate at the same concentrations was found to inhibit growth. Methyl phosphonate possessed good 31P-NMR characteristics for use as a pH probe in Dictyostelium. The entry of methyl phosphonate into the cytoplasm required about 150 min of incubation before an equilibrium was reached with added extracellular methyl phosphonate. A semilogarithmic plot of the efflux of methyl phosphonate out of the amoebae was linear as a function of time, and the kinetic first-order constant was k = 0.016 min-1. The kinetic parameters were consistent with an uptake of methyl phosphonate by fluid-phase pinocytosis. The pH calculated from the chemical shift of the internalized methyl phosphonate signal was found to be pH 7.4 in aerobic Dictyostelium amoebae. The intracellular methyl phosphonate environment turned more acidic in response to anaerobiosis (delta pH = 0.8) or in the presence of a weak acid such as propionate. These pH determinations were in agreement with the values of cytosolic pH derived from the chemical shift of Pi. Methyl phosphonate should be a useful probe for pH measurements in 31P-NMR studies of Dictyostelium in situations where the signal of Pi cannot be attributed with certainty.
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PMID:Methyl phosphonate as a 31P-NMR probe for intracellular pH measurements in Dictyostelium amoebae. 250 63

Dictyostelium discoideum amebae chemotax toward folate during vegetative growth and toward extracellular cAMP during the aggregation phase that follows starvation. Stimulation of starving amebae with extracellular cAMP leads to both actin polymerization and pseudopod extension (Hall et al., 1988, J. Cell. Biochem. 37, 285-299). We have identified an actin nucleation activity (NA) from starving amebae that is regulated by cAMP receptors and controls actin polymerization (Hall et al., 1989, J. Cell Biol., in press). We show here that NA from vegetative cells is also regulated by chemotactic receptors for folate. Our studies indicate that NA is an essential effector in control of the actin cytoskeleton by chemotactic receptors. Guided by a recently proposed model for signal transduction from the cAMP receptor (Snaar-Jagalska et al., 1988, Dev. Genet. 9, 215-225), we investigated which of three signaling pathways activates the NA effector. Treatment of whole cells with a commercial pertussis toxin preparation (PT) inhibited cAMP-stimulated NA. However, endotoxin contamination of the PT appears to account for this effect. The synag7 mutation and caffeine treatment do not inhibit activation of NA by cAMP. Thus, neither activation of adenylate cyclase nor a G protein sensitive to PT treatment of whole cells is necessary for the NA response. Actin nucleation activity stimulated with folate is normal in vegetative fgdA cells. However, cAMP suppresses rather than activates NA in starving fgdA cells. This indicates that the components of the actin nucleation effector are present and that a pathway regulating the inhibitor(s) of nucleation remains functional in starving fgdA cells. The locus of the fgdA defect, a G protein implicated in phospholipase C activation, is directly or indirectly responsible for transduction of the stimulatory chemotactic signal from cAMP receptors to the nucleation effector in Dictyostelium.
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PMID:Transduction of the chemotactic signal to the actin cytoskeleton of Dictyostelium discoideum. 251 Oct 51

Two classes of early genes in Dictyostelium are differentially regulated by extracellular pulses of cAMP interacting with its cell-surface receptor, conditions that also regulate chemotaxis and aggregation. The pulse-repressed genes, such as K5, are induced shortly after the onset of starvation and are repressed a few hr later during aggregation by cAMP pulses. The pulse-induced genes (including D2, M3, and those encoding contact sites A, the G alpha protein subunit G alpha 2, and the cell-surface cAMP receptor) are maximally induced just prior to aggregation by pulses of cAMP and are subsequently repressed by sustained moderate levels of cAMP--conditions that exist sequentially in development. In this manuscript, we further analyze the requirement for cAMP pulses and characterize a requirement for protein synthesis for the expression of these two classes of genes. Our results indicate that the control of expression of both the pulse-induced and pulse-repressed genes requires other developmentally regulated factors in addition to starvation and cAMP pulses. We also identified another early gene, F9, whose expression is stimulated upon starvation, is not responsive to cAMP, and is hyperstimulated by cycloheximide, in a manner similar to the cycloheximide stimulation of c-fos and other serum-induced genes in mammalian cells. Examination of the kinetics of expression of the pulse-induced genes in a mutant blocked in the cAMP relay pathway indicates that their expression is controlled by a two-phase process. The first phase requires starvation and CMF, an extracellular conditioned medium factor, and results in a low level of expression. The second phase requires establishment of the cAMP signal-relay system and induces the genes to a high level. Both phases require prior and concomitant protein synthesis. Some of the members of the pulse-induced class encode elements of the cAMP signal-relay system that controls aggregation, indicating a feedback autoregulation. The two-phase process might allow the "finetuning" of the level of expression of genes involved in aggregation.
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PMID:Two-phase regulatory pathway controls cAMP receptor-mediated expression of early genes in Dictyostelium. 253 21

We have characterized a cDNA and the corresponding gene for a cyclic AMP-inducible gene expressed during Dictyostelium development. This gene, BP74, was found to be first expressed about the time of aggregate formation, approximately 6 h after starvation. Accumulation of BP74 mRNA did not occur in Dictyostelium cells that had been starved in fast-shaken suspension cultures but was induced in similar cultures to which cyclic AMP pulses had been added. The BP74 cDNA and gene were characterized by DNA sequence analysis and transcriptional mapping. When the BP74 promoter region was fused with a chloramphenicol acetyltransferase reporter gene and reintroduced into Dictyostelium cells, the transfected chloramphenicol acetyltransferase gene displayed the same developmentally regulated pattern of expression as did the endogenous BP74 gene, suggesting that all of the cis-acting elements required for regulated expression were carried by a 2-kilobase cloned genomic fragment. On the basis of sequence analysis, the gene appeared to encode a protein containing a 20-residue hydrophobic sequence at the amino-terminal end and 26 copies of a 20-amino-acid repeat.
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PMID:Expression and organization of BP74, a cyclic AMP-regulated gene expressed during Dictyostelium discoideum development. 255 85

A temperature-sensitive mutant of Dictyostelium discoideum has been isolated based on its lack of chemotaxis toward cyclic AMP at the restrictive temperature, 27 degrees C. The mutant develops normally at the permissive temperature, 22 degrees C, but fails to aggregate or complete development at the restrictive temperature. The temperature-sensitive phenotype can be bypassed by allowing cultures to grown into late log phase or to starve for 60-90 min at 22 degrees C prior to a shift to 27 degrees C. At 27 degrees C, the mutant overproduces cell surface cyclic AMP receptors of both high and low affinity and is capable of spontaneous oscillations in light scattering in cell suspensions. Despite its complete lack of morphological development, the mutant undergoes extensive biochemical differentiation. At the onset of starvation, it shows increased levels of N-acetylglucosaminidase, it express cyclic AMP receptors at the normal time and, although somewhat slowly, suppresses those receptors as if aggregation had been achieved. Metabolic pulse labellings with [35S]methionine revealed that the mutant at 27 degrees C displays the same changes in the patterns of newly synthesized proteins observed during the vegetative-to-aggregation and the aggregation-to-slug stages of normal development. The only clear difference from wild type was the failure of the culmination-stage isozyme of beta-glucosidase to appear. The mutant is defective in establishment of intercellular cohesion mechanisms, correlated with poor agglutination by concanavalin A, at the restrictive temperature. The properties of the mutant place severe constraints on models regarding the role of chemoreception and intercellular cohesion in regulation of gene expression.
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PMID:Biochemical differentiation in a mutant of Dictyostelium discoideum defective in cyclic AMP chemotaxis and in intercellular cohesion. 256 Jul 9

We identified signals that affect mRNA levels complementary to a gene that is highly expressed in vegetative Dictyostelium discoideum cells. This gene has been cloned as cDNA in the plasmid pcD-D2. The level of transcripts homologous to pcD-D2 fell dramatically in strain XP55 during the aggregation stage of development when cells differentiate on agar. The level, however, did not fall simply as a result of starvation or aggregation-specific cell contact. Rather, before the level is reduced cells must be deprived of amino acids and cyclic AMP administered in amounts and at intervals in pulses to mimic cyclic AMP signal-relay in aggregation. This effect can be blocked either with cyclic AMP-S (a non-hydrolysable cyclic AMP analogue) or adenosine, both of which prevent cyclic AMP binding to the cyclic AMP cell surface receptor. It is also blocked in 'frigid' aggregation-deficient mutants HC85 and HC112 known to be defective in a G alpha protein. We conclude that the transcript level is balanced by positive nutritional signals acting against negative signals transduced in part through a cell surface cyclic AMP receptor.
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PMID:Regulatory signals affecting a selective loss of mRNA in Dictyostelium discoideum. 256 Nov 27

The arginine-independent, de novo biosynthetic pathway of pyrimidines in Dictyostelium discoideum is initiated by a class II carbamoyl-phosphate synthetase (EC 6.3.5.5) specific for pyrimidine biosynthesis which utilized L-glutamine as its N donor and was partially inhibited by both UTP and CTP. The second step in the de novo pathway was provided by an unregulated aspartate transcarbamoylase (EC 2.1.3.2) which primarily appeared as a multimeric enzyme of 105 kilodaltons. The next enzyme, dihydroorotase (EC 3.5.2.3), was approximately 90-100 kilodaltons. Although the early enzymatic activities of the pyrimidine pathway appeared to reside in independent protein complexes, various unstable molecular species were observed. These structural variants may represent proteolytic fragments of a multienzyme complex. In addition to de novo synthesis, the amoeba demonstrated the capacity for salvage utilization of uracil, uridine, and cytidine. Upon starvation on a solid substratum, axenically grown amoebas began a concerted developmental program accompanied by a restructuring of nucleotide metabolism. The absolute levels of the ribonucleotide pools droppedby 98% within 30 h; however, both the adenylate energy charge and the GTP/ATP ratios were maintained for 50 h after the initiation of development. The maintenance of these metabolic energy parameters required the tight cell-cell contact necessary for development, and the capacity for pyrimidine metabolism was maintained throughout developmental morphogenesis.
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PMID:Characterization of pyrimidine metabolism in the cellular slime mold, Dictyostelium discoideum. 256 62

The relationship between proliferation and differentiation in Dictyostelium discoideum Ax-2 was analyzed with reference to the cell-cycle position at the onset of starvation, using cells synchronized by temperature shift (11.5 degrees C-22.0 degrees C). To examine how far Ax-2 cells at any particular phase of the cell cycle are able to progress through the cycle in response to nutritional deprivation, we measured temporal changes in cell number and nuclearity after starvation. Nuclear DNA synthesis in synchronously developing cells was also monitored by pulse-labeling with [methyl-3H]thymidine. Increase in cell number and subsequent DNA synthesis occurred in cells just before mitosis (referred to as T0.5 cells and T1 cells; 0.5 h and 1 h after the shift-up from 11.5 degrees C to 22.0 degrees C respectively), but not in T3, T5, or T7 cells. When T1 cells were incubated for 6 h in the absence of external nutrients, they (T1 + 6 cells) exhibited developmental features similar to T7 cells, which most rapidly acquired chemotactic sensitivity to 3',5'-cyclic adenosine monophosphate (cAMP) and EDTA-resistant cohesiveness after starvation. Thus, it is quite likely that Ax-2 cells may progress through the cell cycle to a particular point (possibly the cell-cycle position of T7 cells), irrespective of the presence or absence of nutrients, and enter the differentiation phase from this point under conditions of nutritional deprivation. There was no difference in the ratio of prestalk to prespore cells in migratory pseudoplasmodia derived from cells that had been starved at other cell-cycle positions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transition of starving Dictyostelium cells to differentiation phase at a particular position of the cell cycle. 261 67

We have previously shown binding of a monoclonal antibody MUD 9 to the cell surface of Dictyostelium discoideum amoebae and slug cells. In the slug stage the prestalk region was predominantly labelled, while vegetative amoebae showed a great heterogeneity in binding. In the present paper it is shown that the heterogeneous label of vegetative amoebae is due to differences in MUD 9 binding by cells in different cell cycle phases. Cells were synchronized by dilution from stationary phase and the level of MUD 9 binding was determined. Synchrony was determined by investigating increase in cell number and changes in the volume distribution of the cells, and by estimating the number of cells in S phase by monitoring bromodeoxyuridine (BUdR) incorporation. Simultaneously the amount of MUD 9 binding was determined by quantitative microscopy and flow cytometry. The amount of MUD 9 label varies during the cell cycle. The highest amount of label is found on cells early in the cell cycle, i.e. S-phase. These results support the finding that the developmental fate of Dictyostelium discoideum cells depends among other things on the cell cycle position of the cells at the moment of starvation.
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PMID:Expression of a cell surface antigen in Dictyostelium discoideum in relation to the cell cycle. 261 58

During early starvation-induced development, amoebae of Dictyostelium discoideum have been previously shown to increase sulfation and fucosylation of glycoprotein-linked oligosaccharides to levels above those observed in axenically growing cells. We report here that the axenic broth culture itself induces generation of high levels of fucosylated glycoprotein-linked oligosaccharides at all stages in the growth curve. However, when grown on bacteria, amoebae of both the axenic strain and the wild type show dramatic depression in fucose incorporation during early exponential growth. In mid- and late-exponential stages of growth, fucosylation rises to the levels found at all stages of axenic culture. Sulfation also increases during early development, but, in contrast to fucosylation, oligosaccharide sulfation is not altered by growth in axenic medium and does not increase during growth on bacteria. Starvation of bacterially grown cells results in increased sulfation and a further rise in fucosylation, as is also characteristic of broth-grown cells. The ability of axenic culture to uncouple control of these two classes of glycan-modification steps suggests that the synchronous increases during early development actually reflect responses to different regulatory signals, even though they participate in the same metabolic process. The increase in in vivo fucosyltransferase activity, which can act on many substrate glycoproteins, may alter many characteristics of the cells.
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PMID:Differential regulation of glycoprotein sulfation and fucosylation during growth of Dictyostelium discoideum. 274 70


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