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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PhoR of Bacillus subtilis is a histidine sensor-kinase belonging to the family of two-component signal transduction systems. PhoR is responsible for processing the phosphate-starvation signal and providing phosphate input to regulate the level of phosphorylated response regulator, PhoP, which activates/represses Pho regulon gene transcription. The catalytic domain of PhoR is sufficient for the low-phosphate inducible expression of Pho regulon genes since removing the N-terminal membrane-associated domain did not alter the kinetics of Pho induction, albeit the total level of induction was decreased (1). In this study we showed that the complete B. subtilis PhoR protein produced in Escherichia coli can be reverse phosphorylated by PhoP-phosphate. We also used a C-terminal fragment of the PhoR protein, PhoR, to demonstrate that the phosphoryl group on phospho-PhoP was transferred back to PhoR in the reverse phosphorylation reaction or released as inorganic phosphate to the reaction mixture. The reverse phosphorylation of the PhoR protein likely occurs at the same histidine residue (His360) that is utilized for the autokinase reaction by the same protein. In the presence of ADP, the phosphoryl group is further transferred to ADP to form ATP. While the autokinase reaction, the forward phosphotransfer reaction from PhoR approximately P to PhoP, and the release of inorganic phosphate from PhoP approximately P in the presence of PhoR require Mg(2+), the reverse phosphotransfer from PhoP approximately P to PhoR does not. These results indicate that the energy levels of the phosphoryl groups on PhoP and PhoR are very similar. The reversible autokinase reaction and/or the reversible phosphotransfer reaction between PhoR approximately P and PhoP may have a role in PhoP approximately P decay thus influencing the PhoP approximately P concentration in the cell.
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PMID:Decay of activated Bacillus subtilis pho response regulator, PhoP approximately P, involves the PhoR approximately P intermediate. 1043 20

Apoptosis in neuronal tissue is an efficient mechanism which contributes to both normal cell development and pathological cell death. The present study explored the effects of extracellular ATP on starvation-induced apoptosis in rat pheochromocytoma PC12 cells. Incubation of differentiated PC12 cells with ATP for 6h suppressed apoptosis. 2-Methylthio-ATP, a P2 purinoceptor agonist, was as potent as ATP in suppressing apoptosis, whereas adenosine, ADP, alpha,betamethylene-ATP or UTP was totally ineffective. The suppressive action of ATP was dependent upon the presence of extracellular Ca2+ and blocked by co-incubation with the P2 antagonist, suramin. DNA ladder formation, a typical symptom of apoptosis in starved cells, was inhibited by ATP, 2-methylthio-ATP but not by UTP. These results suggest that the inhibitory action of extracellular ATP on apoptotic cell death is mediated via the activation of P2X2 receptors in differentiated PC12 cells.
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PMID:Extracellular ATP inhibits starvation-induced apoptosis via P2X2 receptors in differentiated rat pheochromocytoma PC12 cells. 1080 82

Inorganic polyphosphate (poly P) is a chain of tens or many hundreds of phosphate (Pi) residues linked by high-energy phosphoanhydride bonds. Despite inorganic polyphosphate's ubiquity--found in every cell in nature and likely conserved from prebiotic times--this polymer has been given scant attention. Among the reasons for this neglect of poly P have been the lack of sensitive, definitive, and facile analytical methods to assess its concentration in biological sources and the consequent lack of demonstrably important physiological functions. This review focuses on recent advances made possible by the introduction of novel, enzymatically based assays. The isolation and ready availability of Escherichia coli polyphosphate kinase (PPK) that can convert poly P and ADP to ATP and of a yeast exopolyphosphatase that can hydrolyze poly P to Pi, provide highly specific, sensitive, and facile assays adaptable to a high-throughput format. Beyond the reagents afforded by the use of these enzymes, their genes, when identified, mutated, and overexpressed, have offered insights into the physiological functions of poly P. Most notably, studies in E. coli reveal large accumulations of poly P in cellular responses to deficiencies in an amino acid, Pi, or nitrogen or to the stresses of a nutrient downshift or high salt. The ppk mutant, lacking PPK and thus severely deficient in poly P, also fails to express RpoS (a sigma factor for RNA polymerase), the regulatory protein that governs > or = 50 genes responsible for stationary-phase adaptations to resist starvation, heat and oxidant stresses, UV irradiation, etc. Most dramatically, ppk mutants die after only a few days in stationary phase. The high degree of homology of the PPK sequence in many bacteria, including some of the major pathogenic species (e.g. Mycobacterium tuberculosis, Neisseria meningitidis, Helicobacter pylori, Vibrio cholerae, Salmonella typhimurium, Shigella flexneri, Pseudomonas aeruginosa, Bordetella pertussis, and Yersinia pestis), has prompted the knockout of their ppk gene to determine the dependence of virulence on poly P and the potential of PPK as a target for antimicrobial drugs. In yeast and mammalian cells, exo- and endopolyphosphatases have been identified and isolated, but little is known about the synthesis of poly P or its physiologic functions. Whether microbe or human, all species depend on adaptations in the stationary phase, which is truly a dynamic phase of life. Most research is focused on the early and reproductive phases of organisms, which are rather brief intervals of rapid growth. More attention needs to be given to the extensive period of maturity. Survival of microbial species depends on being able to manage in the stationary phase. In view of the universality and complexity of basic biochemical mechanisms, it would be surprising if some of the variety of poly P functions observed in microorganisms did not apply to aspects of human growth and development, to aging, and to the aberrations of disease. Of theoretical interest regarding poly P is its antiquity in prebiotic evolution, which along with its high energy and phosphate content, make it a plausible precursor to RNA, DNA, and proteins. Practical interest in poly P includes many industrial applications, among which is the microbial removal of Pi in aquatic environments.
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PMID:Inorganic polyphosphate: a molecule of many functions. 1087 45

In the C(4) plant maize (Zea mays L.), two ferredoxin isoproteins, Fd I and Fd II, are expressed specifically in mesophyll and bundle-sheath cells, respectively. cDNAs for these ferredoxins were introduced separately into the cyanobacterium Plectonema boryanum with a disrupted endogenous ferredoxin gene, yielding TM202 and KM2-9 strains expressing Fd I and Fd II. The growth of TM202 was retarded under high light (130 micromol/m(2)/s), whereas KM2-9 grew at a normal rate but exhibited a nitrogen-deficient phenotype. Measurement of photosynthetic O(2) evolution revealed that the reducing power was not efficiently partitioned into nitrogen assimilation in KM2-9. After starvation of the cells in darkness, the P700 oxidation level under far-red illumination increased significantly in TM202. However, it remained low in KM2-9, indicating an active cyclic electron flow. In accordance with this, the cellular ratio of ATP/ADP increased and that of NADPH/NADP(+) decreased in KM2-9 as compared with TM202. These results demonstrated that the two cell type-specific ferredoxins differentially modulate electron flow around photosystem I.
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PMID:Differential electron flow around photosystem I by two C(4)-photosynthetic-cell-specific ferredoxins. 1101 7

Extracellular ATP suppressed the growth of HL-60 leukemia cells and induced their differentiation as revealed by N-formyl-methionyl-leucyl-phenylalanine-induced beta-glucuronidase release. ATP degraded to ADP, AMP, and adenosine, and the effect of ATP on cell growth was mimicked by these metabolites added to the cultures. The stable analog alpha,beta-methylene ATP, however, had only a weak inhibitory effect on cell growth. Adenine nucleotide-induced growth suppression was reversed by uridine, suggesting the involvement of intracellular pyrimidine starvation secondary to adenosine accumulation. Consistent with this, ATP induced intracellular starvation of pyrimidine nucleotides, and this effect was also prevented by pretreatment of cells with uridine. The order of effectiveness of ATP-induced differentiation of HL-60 cells, unlike that for growth suppression, was ATP > ADP > AMP, and adenosine had no effect. Furthermore, uridine had no effect and the stable analog, alpha,beta-methylene ATP also induced HL-60 cell differentiation, suggesting that differentiation was due to ATP per se. We tested the hypothesis that ATP-induced differentiation arises from activation of adenylyl cyclase by the novel P2Y(11) receptor using the cell-permeable inhibitor of protein kinase A, Rp-CPT-cAMPS (8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate, Rp isomer). Rp-CPT-cAMPS (1-100 microM) prevented ATP-induced differentiation of HL-60 cells as assessed by fMLP-induced beta-glucuronidase release. However, Rp-CPT-cAMPS did not prevent ATP-induced growth suppression. Taken together, the data indicate that extracellular ATP suppresses HL-60 growth and induces their differentiation by distinct mechanisms. Growth suppression arises from adenosine generation and consequent pyrimidine starvation. Differentiation arises, at least in part, from a distinct mechanism involving the activation of cell surface P2 receptors coupled to cAMP generation and activation of protein kinase A.
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PMID:Extracellular ATP-dependent suppression of proliferation and induction of differentiation of human HL-60 leukemia cells by distinct mechanisms. 1107 40

The specific activity and the kinetic properties of partly purified pyruvate kinase (PK) (EC 2.7.1.40) from the Northern Krill, Meganyctiphanes norvegica, were investigated in relation to varying food resources. In order to evaluate the effect of starvation on the total energy metabolism, the respiration rates of fed and unfed krill were determined. The FPLC-elution profile of PK displayed two distinct peaks - PK I and II. The first isoform represented 80% of the total PK activity in the organism, and 20% was contributed by the second isoform. PK I was inhibited by ATP but was not influenced by fructose-1,6-bisphosphate (FBP). In contrast, PK II showed ATP inhibition and up to 2.5-fold increased activity by addition of 17 micromol.l(-1) FBP. The Michaelis-Menten constants of both isoforms were 2-10-fold higher for ADP than for phosphoenolpyruvate (PEP). Alanine showed no regulatory effect on PK I and II. In specimens starved for 7 days oxygen consumption decreased by 20%. Neither the feeding experiments nor the animals captured in the field during low and high productive seasons indicate that PK properties of M. norvegica are modified in relation to food supply. Accordingly, alternative mechanisms are involved in the depression of the metabolic rate in terms of oxygen consumption.
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PMID:Studies on metabolic properties in the Northern Krill, Meganyctiphanes norvegica (Crustacea, euphausiacea): influence of nutrition and season on pyruvate kinase. 1115 47

The CDC25 gene product is a guanine nucleotide exchange factor for Ras proteins in yeast. Recently it has been suggested that the intracellular levels of guanine nucleotides may influence the exchange reaction. To test this hypothesis we measured the levels of nucleotides in yeast cells under different growth conditions and the relative amount of Ras2-GTP. The intracellular GTP/GDP ratio was found to be very sensitive to growth conditions: the ratio is high, close to that of ATP/ADP during exponential growth, but it decreases rapidly before the beginning of stationary phase, and it drops further under starvation conditions. The addition of glucose to glucose-starved cells causes a fast increase of the GTP/GDP ratio. The relative amount of Ras2-GTP changes in a parallel way suggesting that there is a correlation with the cytosolic GTP/GDP ratio. In addition 'in vitro' mixed-nucleotide exchange experiments done on purified Ras2 protein demonstrated that the GTP and GDP concentrations influence the extent of Ras2-GTP loading giving further support to their possible regulatory role.
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PMID:Role of guanine nucleotides in the regulation of the Ras/cAMP pathway in Saccharomyces cerevisiae. 1133 89

Since extracellular ATP can exhibit cytotoxic activity in vivo and in vitro, its application has been proposed as an alternative anticancer therapy. In this study we investigated the mechanisms of ATP-induced cytotoxicity in a human leukemic cell line (U-937). ATP added as a single dose exceeding 50 microM was cytostatic or even cytotoxic for U-937 cells. Interestingly, growth inhibition by ATP (50-3500 microM) showed a biphasic dose response. Up to 800 microM, ATP was cytotoxic in a dose-dependent manner (EC(50) 90 microM). In a range between 800 and 2500 microM, cell count was markedly higher despite the higher ATP concentrations. The cytotoxic effect of ATP could be antagonized by addition of uridine as a pyrimidine source and, alternatively, by addition of the nucleoside transmembrane inhibitor dipyridamole. The apoptosis-inducing adenosine A(3) receptor was not involved in measurable quantities, since (1) adenosine did not lead to an elevation of intracellular calcium levels, and (2) an unselective A(1-3) antagonist (ULS-II-80) could not abrogate the cytotoxic effect. Experiments monitoring extracellular nucleotide metabolism confirmed the assumption that the long-term production and continuous uptake of adenosine, which is extracellularly generated by degradation of ATP, led to an intracellular nucleotide imbalance with pyrimidine starvation. The biphasic dose response to higher ATP concentrations could be explained by the rapid degradation of lower ATP concentrations (300 microM) to adenosine by serum-derived enzymes, whereas higher concentrations (900 microM) only produced small amounts of adenosine due to forward inhibition of AMP hydrolysis by prolonged high ADP levels. FACS analysis revealed that at lower adenosine concentrations (300 microM) a reversible G(1) phase arrest of the cell cycle was induced, whereas higher concentrations (1000 microM) triggered apoptosis. Considering ATP as a potential cytostatic drug, our data have important implications concerning metabolic interactions of administered nucleotides.
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PMID:Biphasic cytotoxic mechanism of extracellular ATP on U-937 human histiocytic leukemia cells: involvement of adenosine generation. 1133 90

ATP, UTP, ADP and UDP induced intracellular Ca(2+) responses and oscillations in HeLa cells that sometimes lasted over 1 h. The response is due to the activation of P2Ys, G-protein coupled ATP receptors, because the oscillations persisted for several minutes even in Ca(2+)-free solution, and suramin and PPADS, antagonists of ATP receptors, partially inhibited the response. The potency of these nucleotides varied with the culture or cell conditions, i.e. UTP was generally most potent but in some cases UDP was more potent; responses to UDP were variable while those to ATP were constant. In addition, Ca(2+) responses to ATP and UDP were additive. These findings suggested the existence of two or more subtypes of P2Ys in HeLa cells. RT-PCR experiments revealed the existence of P2Y(2), P2Y(4) and P2Y(6). Recovery from starvation (culture in FBS-free medium overnight and re-addition of FBS) increased the responses to UTP and UDP but not to ATP, suggesting that the number or activity of P2Y(6) and/or P2Y(4) receptors may increase with cell proliferation in HeLa cells.
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PMID:ATP-induced calcium oscillations and change of P2Y subtypes with culture conditions in HeLa cells. 1257 23

The roots of alternate-bearing citrus (Murcott, a Citrus reticulata hybrid) trees undergo extreme fluctuations of carbohydrate abundance and starvation. Using this system, we investigated the effect of root carbohydrate (total soluble sugar, sucrose and starch) depletion on carbohydrate-related gene expression. A series of genes, including those coding for starch phosphorylase ( STPH-L and STPH-H), ADP-glucose pyrophosphorylase, small subunit ( Agps), R1, plastidic ADP/ATP transporter ( AATP), phosphoglucomutase ( PGM-P and PGM-C), sucrose synthase ( CitSuS1 and CitSuSA), sucrose transporter ( SUT1 and SUT2), hexokinase ( HK) and alpha-amylase ( alpha-AMY), have been isolated and their expression analyzed. The genes were found to respond differentially to carbohydrate depletion. STPH-L, STPH-H, Agps, R1, AATP, PGM-P, PGM-C, CitSuS1 and HK were down-regulated while SUT1 and alpha-AMY were up-regulated during carbohydrate depletion. Two other genes, CitSuSA and SUT2, did not respond to carbohydrate depletion. Fruit removal, which interrupted the carbohydrate depletion induced by heavy fruiting, reversed these gene expression patterns. Trunk girdling and whole-plant darkening treatments, which brought about root carbohydrate depletion, induced the same changes in gene expression obtained in the alternate-bearing system. The possible roles of the up- and down-regulated genes in the metabolism of carbohydrate-depleted citrus roots are discussed. Although the specific signals involved have not been determined, the results support the feast/famine hypothesis of carbohydrate regulation proposed by Koch [K.E. Koch (1996) Annu Rev Plant Physiol Plant Mol Biol 47:509-540].
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PMID:Effects of carbohydrate starvation on gene expression in citrus root. 1272 44


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