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)

(6R)-5,10-Dideaza-5,6,7,8-tetrahydrofolic acid [(6R)DDATHF] is a folate antimetabolite with activity specifically directed against de novo purine synthesis, primarily through inhibition of glycinamide ribonucleotide transformylase. This inhibition resulted in major changes in the size of the nucleotide pools in CCRF-CEM cells. After a 4-h incubation with 1 microM (6R)DDATHF, dramatic reductions in the ATP and GTP pools were observed, with almost no effect on CTP, UTP, and deoxyribonucleotide pools. When the incubation was continued in drug-free medium, recovery of ATP and GTP pools was protracted. ATP did not return to normal until 24-36 h, and GTP pools were only partially repleted by 48 h. The ATP and GTP pools were not affected when the initial 4-h incubation with (6R)DDATHF was conducted in the presence of 100 microM hypoxanthine. Addition of hypoxanthine to the medium after a 4-h incubation with (6R)DDATHF caused rapid recovery of the ATP and GTP pools. Similar effects were seen when the purine precursor aminoimidazole carboxamide was used in place of hypoxanthine. The effect of (6R)DDATHF on nucleotide pools and the capability of hypoxanthine or aminoimidazole carboxamide to prevent or reverse this phenomenon correlated directly with the inhibition of cell growth. Presumably as a consequence of the decrease in purine nucleotide triphosphate levels, the conversion of exogenously added uridine, thymidine, and deoxyuridine to nucleotides was markedly decreased. These effects were protracted for almost 48 h and were also reversed by hypoxanthine. Differential repletion of ATP and GTP pools after (6R)DDATHF pre-treatment demonstrated that diminished precursor phosphorylation is primarily a consequence of GTP rather than ATP starvation.
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PMID:(6R)-5,10-Dideaza-5,6,7,8-tetrahydrofolic acid effects on nucleotide metabolism in CCRF-CEM human T-lymphoblast leukemia cells. 170 49

In patients with heart failure there are distinct functional abnormalities in the myocytes themselves. This review deals with the deteriorations in the myocardial energy metabolism and the recently found alterations in the neurohumoral and hormonal signal transduction and signal realization within the cardiac cells. Beside the reduction in the volume of mitochondria in the overloaded myocardium the energy starvation is also reflected by a decrease in the content of high energy phosphates. Studies on nonfailing and failing human ventricular myocardium identified significant alterations in the neurohumoral regulation of the heart including the fluxes and the transport processes of Ca2+ as well as the beta-adrenoceptors, G-proteins, cAMP levels and cAMP-mediated processes. Recent data on the existence of auto-antibodies against the ADP/ATP translocator of the mitochondrial membrane and of stimulatory acting autoantibodies against i) the L-type calcium channel and ii) the beta 1-adrenoceptor, respectively, in patients with dilated cardiomyopathy, may open a new view in the etiology of heart failure and for consequences in the therapeutic concept of these diseases.
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PMID:[Cellular and molecular mechanisms in heart failure]. 172 87

1. Yeast tRNA nucleotidyl transferase is inhibited by low molecular weight compounds present in cell-free extracts. The inhibition produced by the main component(s) is competitive with respect to ATP and is not prevented by metal chelating agents. The major component(s) has been partially purified. It is resistant to heat (90 degrees C, 5 min) and insensitive to digestion by alkaline phosphatase, snake venom phosphodiesterase and inorganic pyrophosphatase, indicating that it is not a nucleotide. 2. Besides the masking of the transferase activity in the crude extracts by the inhibitors, the enzyme is inactivated in nitrogen starved cells. The inactivation also occurs in yeast mutants lacking several proteases and is not prevented by inhibitors of yeast proteases. These results rule out extracellular proteolysis as the cause of inactivation and strength our previous observations on the metabolic inactivation of the transferase in response to nitrogen starvation.
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PMID:Characteristics of the inhibition and metabolic inactivation of the yeast TRNA nucleotidyl transferase. 177 53

1. The effects of altering metabolism on Na(+)-K(+)-Cl- co-transport were studied in ferret red cells. Na(+)-K(+)-Cl- co-transport was measured as the bumetanide-sensitive uptake of 86Rb. 2. Glucose, but not inosine or adenosine, sustained metabolism and maintained cell ATP content ([ATP]i) at the physiological level. [ATP]i could be reduced by prolonged incubation of cells in a substrate-free medium or more quickly by incubating cells with 2-deoxyglucose or with a mixture of iodoacetamide and glucose. 3. Na(+)-K(+)-Cl- co-transport activity was inhibited when [ATP]i was reduced to below 100 mumol (1 cell)-1 by starvation or by treatment with 2-deoxyglucose. However, a unique relationship between [ATP]i and activity could not be found. [ATP]i and the method and time course of ATP depletion all influenced activity. The inhibition of Na(+)-K(+)-Cl- co-transport, caused by reducing [ATP]i could be partially reversed by restoring [ATP]i to normal. 4. Increasing the concentration of intracellular ionized magnesium [( Mg2+]i) did not stimulate co-transport activity in ATP-depleted cells. This contrasts with the substantial stimulation seen in cells with normal [ATP]i. 5. Vanadate stimulated Na(+)-K(+)-Cl- co-transport activity in ATP-depleted cells but not in cells with normal [ATP]i. Fluoride did not affect activity at any [ATP]i. 6. The effects of some sulphydryl reagents on Na(+)-K(+)-Cl- co-transport were also examined. n-Ethylmaleimide (1 mM) inhibited Na(+)-K(+)-Cl- co-transport while it stimulated bumetanide-resistant potassium transport. Dithiothreitol (1 mM) did not affect activity. Iodoacetamide (6 mM) appeared to reduce the inhibition of cotransport activity seen at low [ATP]i but also greatly increased cell fragility. 7. The data suggest that activity of the Na(+)-K(+)-Cl- co-transport system is controlled by a cycle of phosphorylation and dephosphorylation with the phosphorylated form being active. Phosphorylation and transport appear to be almost maximal in ferret red cells with normal [ATP]i. Reduction of [ATP]i may allow changes in phosphatase activity to manifest as changes in transport rate. Differences in the balance between phosphorylation and dephosphorylation may explain tissue-dependent variations in the response of the system to various stimuli.
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PMID:The effects of metabolism on Na(+)-K(+)-Cl- co-transport in ferret red cells. 189 Jun 46

Structure-functional transformation fo respiratory chain, developed in response to 72 hrs starvation involved the following alterations: 1. in mitochondria of starved rats distinct increase ws observed in sensitivity of palmitocarnitine oxidation, but not of succinate, to benzhydroxamic acid--chelator of non-heme iron; 2. as compared with controls accumulation of malonic dialdehyde was completely inhibited in liver mitochondria of the starved rats in presence of benzhydroxamic acid; 3. considerable alteration in sensitivity of respiration and ATP synthesis to the effect of some inhibitors was found in liver mitochondria of starved rats. Results of the experiment are discussed on the basis of the assumption that existence of additional pathways of ATP synthesis, essential for adaptation-restoration processes, is biologically important under conditions of stress.
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PMID:[Features of oxidation of reserve lipids in liver mitochondria during starvation: the role of non-heme iron and free radical fatty acid oxidation]. 194 86

The activities of monoamine oxidase (MAO), responsible for oxidative deamination of many biogenic amines, and Na+, K(+)-ATPase, which plays a crucial role in the release mechanism of neurotransmitters, were determined in rat brain after acute starvation. They were assayed biochemically from four different regions of the brain in two subcellular fractions. Acute starvation decreased the activity of MAO, whereas the Na+,K(+)-ATPase activity was increased. An effect of starvation was also seen on the blood glucose level, body wt, and the protein content of different brain regions. Starvation or normal dietary fluctuations of certain nutrients that exert precursor influence over neurotransmitter synthesis are important to the brain, and contribute to its regulation of both neuroendocrine response and behavior. A rise in the substrate level, i.e., ATP, as a result of increased utilization of ketone bodies and low level of monoamines in the brain after acute starvation, may be the underlying factor for increasing the activity of Na+,K(+)-ATPase in rat brain. These results suggest that, probably, certain adaptive mechanisms become operative in the brain under disturbed physiological conditions.
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PMID:Effect of acute starvation on monoamine oxidase and Na+,K(+)-ATPase activity in rat brain. 196 2

31P-NMR spectroscopy has been used to study the energy metabolism and the NMR visibility of ATP and intracellular Pi of the C6 glioma cell line and rat astrocyte grown on microcarrier beads with the following results. 1. In vivo NMR spectra of C6 glioma cells and rat astrocytes indicate that these cells were able to maintain their level of ATP resonances during a long anoxic period (more than an hour). Both cell types were sensitive to ischemia which induced a loss of ATP resonances within 40 min. Glucose starvation induced by 40% decrease in ATP resonances correlated to a 50% increase in the intensity of the Pi signal. These changes corresponded to a new steady state which could be reversed by reperfusing the cells with a glucose-containing medium. 2. In contrast to in vivo data, 31P-NMR analyses of perchloric acid extracts of cells incubated in a glucose-free medium showed that their ATP and Pi contents were unchanged during starvation. The changes of NMR visibility of the metabolites in living C6 cells were correlated to modifications of their macroscopic longitudinal relaxation times, evolving from 0.30 +/- 0.08 s and 6.6 +/- 1.5 s in the presence of glucose to 0.68 +/- 0.26 s and 3.2 +/- 0.9 s in the absence of glucose for ATP and Pi, respectively. The changes of the NMR detectability of ATP and Pi indicate that changes in their microenvironment occur during glucose starvation, suggesting the existence of different pools of these metabolites within the cells. 3. Under various experimental conditions, i.e. anoxia, ischemia and glucose starvation, rat astrocytes in primary culture showed a very similar behavior to that of C6 cells, suggesting a similar adaptability to the nature of the energy supply for both the normal and the malignant cell.
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PMID:Phosphorus-31 nuclear magnetic resonance of C6 glioma cells and rat astrocytes. Evidence for a modification of the longitudinal relaxation time of ATP and Pi during glucose starvation. 199 80

Interleukin 3 (IL-3) stimulates the growth of various types of hemopoietic progenitors. In vitro, survival of a series of murine cell lines derived from either neoplastic or nonneoplastic hemopoietic tissue shows a strict IL-3 dependence. In order to test the implication of energy metabolism in this dependence as claimed in several studies, intracellular ATP levels as well as accumulative lactate release were measured in the murine hemopoietic lines FDC-P1, 32Dcl.23, DA-1, DA-3, NFS-60, and NFS-78. ATP levels showed little or no changes within 4-6 h of IL-3 starvation. In the absence of IL-3 the accumulative lactate release ranged from 1.4 to 2.6 mM, and in its presence values between 1.5 and 3.4 mM were recorded within 7 h. Only 32Dcl.23 showed an almost complete suppression of lactate release upon IL-3 withdrawal. The cell cycle times of these cell lines determined by flow cytometry ranged between 9 (DA-3) and 24 h (NFS-78). In the presence of IL-3 there was a significant inverse relationship between cell cycle times and lactate production. It is concluded that neither ATP generation nor the metabolic pathway of lactate production, although the latter correlated with proliferative activity in the studied cell lines, is controlled by IL-3. Furthermore, no control by IL-3 of essential amino acid incorporation into proteins was detected in cell lines 32Dcl.23 and NFS-60.
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PMID:Lactate production and amino acid incorporation in interleukin 3-dependent, factor-deprived hemopoietic murine cell lines. 220 20

beta-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of beta-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors alpha 2-macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy-D-glucose and 2,4-dinitrophenol and the omission of Ca2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of beta-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of beta-lipotropin.
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PMID:Processing of the lipid-mobilizing peptide beta-lipotropin in rabbit adipose tissue. 221 32

Ascite tumor cells EL-4 were incubated in conditions of energy starvation (Hanks salt solution with rothenone and without glucose) at 37 degrees C for 3 hours. Under these conditions, some structural cell damages appeared within the first hours: enlarging and flattening of the cells, blebbing, vacuolization of the cytoplasm, nuclear chromatin condensation. Later on, a share of cells with obvious damage decreased, whereas that of the cells stained with trypan blue (dead cells) much increased (up to 90% after a 3 hour incubation). The cellular ATP decreased abruptly (up to 10% of the control) during the first 10 minutes of starvation. Free Ca2+ concentration increased within 1 hour of incubation more than two-fold. The conditions promoting Ca2+ influx (ionophore A23187 + Ca2+ in medium) accelerated the damage and cell death. However, the increase in free Ca2+ concentration did not trigger any damage in the energy-starved cells, since in the Ca2(+)-depleted medium (no increase in free Ca2(+)-concentration) the development of damages was not prevented. The damage initiation was irreversible: the addition of glucose to cell suspensions after 0.5-1 hour of their incubation in energy-starved condition did not prevent the development of damage, while ATP content in these cells was much increased.
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PMID:[The relationship of damage to and death of ascitic tumor cells during starvation to the ATP and free calcium content in the cells]. 226 Feb 24


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