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)

The phorbol ester TPA (phorbol 12-myristate 13-acetate) substitutes for CO2 as an agonist for transforming Trypanosoma cruzi epimastigotes to the metacyclic trypomastigote stage in a starvation medium consisting of phosphate buffered saline + 10 mM proline, 10 mM sodium acetate and 0.035% NaHCO3. Since TPA is thought to stimulate protein kinase C by mimicking the activity of the secondary messenger diacylglycerol, the above result suggested that T. cruzi metacyclogenesis could be activated by a Ca(2+)-dependent protein kinase C signal induction pathway. Accordingly, cytosolic calcium flux ([Ca2+]i) in epimastigotes, activated with 5% CO2 or TPA (10(-7) M), was measured with the Ca2+ molecular probe, fluo-3AM. In addition, [Ca2+]i was measured in cells incubated with putative metacyclogenic agonists (e.g. proline, glutamate, bioamines, ionophores and catecholamines). None of the compounds studies, except for EGTA, affected cytosolic Ca2+ levels. Control assays with 11 microM thapsigargin, which mobilizes noncytoplasmic Ca2+ stores by inhibiting endoplasmic reticulum Ca(2+)-ATPase, validated our fluorometric assay procedure. Although thapsigargin significantly increases cytoplasmic Ca2+ fluorescence, it has no effect on transformation. The protein kinase C inhibitors staurosporine, H-7 and HA 1004 were tested for their effect on T. cruzi metacyclogenesis. Low concentrations of staurosporine and HA 1004 significantly elevated Peru strain transformation while H-7 had no effect on Peru strain metacyclogenesis. Inhibitor H-7 did significantly depress CL transformation. The results indicate that induction of T. cruzi metacyclic trypomastigote formation by CO2 and TPA is not accompanied by changes in cytosolic Ca2+ and do not provide supporting evidence for participation of a protein kinase C-mediated phosphoinositide cascade in metacyclogenesis.
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PMID:Absence of transitory [Ca2+]i flux during early in vitro metacyclogenesis of Trypanosoma cruzi. 846 96

In Escherichia coli, starvation (stationary-phase)-mediated differentiation involves 50 or more genes and is triggered by an increase in cellular sigma s levels. Western immunoblot analysis showed that in mutants lacking the protease ClpP or its cognate ATPase-containing subunit ClpX, sigma s levels of exponential-phase cells increased to those of stationary-phase wild-type cells. Lack of other potential partners of ClpP, i.e., ClpA or ClpB, or of Lon protease had no effect. In ClpXP-proficient cells, the stability of sigma s increased markedly in stationary-phase compared with exponential-phase cells, but in ClpP-deficient cells, sigma s became virtually completely stable in both phases. There was no decrease in ClpXP levels in stationary-phase wild-type cells. Thus, sigma s probably becomes more resistant to this protease in stationary phase. The reported sigma s-stabilizing effect of the hns mutation also was not due to decreased protease levels. Studies with translational fusions containing different lengths of sigma s coding region suggest that amino acid residues 173 to 188 of this sigma factor may directly or indirectly serve as at least part of the target for ClpXP protease.
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PMID:Regulation of Escherichia coli starvation sigma factor (sigma s) by ClpXP protease. 855 Apr 68

During growth on low-K+ medium (1 mM K+), Methanobacterium thermoautotrophicum accumulated K+ up to concentration gradients ([K+]intracellular/[K+]extracellular) of 25,000- to 50,000-fold. At these gradients ([K+]extracellular of < 20 microM), growth ceased but could be reinitiated by the addition of K+ or Rb+. During K+ starvation, the levels of a protein with an apparent molecular weight of 31,000 increased about sixfold. The protein was associated with the membrane and could be extracted by detergents. Cell suspensions of M. thermoautotrophicum obtained after K+-limited growth catalyzed the transport of both K+ and Rb+ with apparent Km and Vmax values of 0.13 mM and 140 nmol/min/mg, respectively, for K+ and 3.4 mM and 140 nmol/min/mg, respectively, for Rb+. Rb+ competitively inhibited K+ uptake with an inhibitor constant of about 10 mM. Membranes of K+-starved cells did not exhibit K+-stimulated ATPase activity. Immunoblotting with antisera against Escherichia coli Kdp-ATPase did not reveal any specific cross-reactivity against membrane proteins of K+-starved cells. Cells of M. thermoautotrophicum grown at a high potassium concentration (50 mM) catalyzed K+ and Rb+ transport at similar apparent Km values (0.13 mM for K+ and 3.3 mM for Rb+) but at significantly lower apparent Vmax values (about 60 nmol/min/mg for both K+ and Rb+) compared with K+-starved cells. From these data, it is concluded that the archaeon M. thermoautotrophicum contains a low-affinity K+ uptake system which is overproduced during growth on low-K+ medium.
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PMID:Low-affinity potassium uptake system in the archaeon Methanobacterium thermoautotrophicum: overproduction of a 31-kilodalton membrane protein during growth on low-potassium medium. 855 May 7

The level of malondialdehyde (MDA), an index of lipid peroxidation, and the antioxidants superoxide dismutase (SOD) and glutathione (GSH), as well as the activity of Na+, K(+)-ATPase, were assessed in whole rat brain after immobilization, anemic hypoxia (NaNO2) and 72 h starvation. The effect of these stressors on plasma glucose and corticosterone levels was also observed. Hypoxia and starvation stimulated the lipid peroxide formation in brain as indicated by an increase in the level of MDA, being higher after starvation than hypoxia. Brain SOD activity was also increased in response to hypoxia and starvation while GSH content was only diminished in hypoxia. However, neither MDA nor antioxidants were affected by immobilization. On the other hand, the activity of brain Na+, K(+)-ATPase was significantly increased by immobilization and hypoxia but decreased in starvation. A similar pattern of change was also observed in plasma glucose and corticosterone levels in response to these stressors. These results elucidate differences in the biochemical response of animals towards various types of stress, with increased lipid peroxide formation in hypoxia and starvation.
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PMID:Effect of various stressors on the level of lipid peroxide, antioxidants and Na+, K(+)-ATPase activity in rat brain. 862 Sep 36

The native V1 complex of the tobacco hornworm vacuolar type ATPase (V-ATPase) was purified from cytosolic extracts of molting larval midgut. It consisted of the established V-ATPase subunits A, B, and E along with the 14-kDa subunit F and the novel 13-kDa subunit G. The final amount of purified V1 complex made up an unexpectedly high 2% of the total cytosolic protein, with a yield of approximately 0.4 mg/g of tissue. An equally high amount of cytosolic V1 complex was obtained from starving intermolt larvae. By contrast, the cytosolic V1 pool was reduced drastically in feeding intermolt larvae or in larvae that had been refed after starvation. The activity of the membrane-bound V-ATPase holoenzyme was inversely related to the size of the cytosolic V1 pool, suggesting that the insect plasma membrane V-ATPase is regulated by reversible disassembly of the V1 complex as a function of the feeding condition of the larvae. Like F1-ATPases, the purified V1 complex exhibited Ca2+-dependent ATPase activity and, in the presence of 25% methanol, exhibited Mg2+-dependent ATPase activity. Therefore, we designate the native V1 complex, V1-ATPase. Both enzyme activities were completely inhibited by micromolar N-ethylmaleimide. In contrast to the Ca2+-dependent V1-ATPase activity, the Mg2+/methanol-dependent V1-ATPase activity did not decrease with the incubation time and thus was not inhibited by ADP. Methanol appears to induce a conformational change of the V1 complex, leading to enzymatic properties of the V1-ATPase that are similar to those of the membrane-bound V-ATPase holoenzyme. This is the first time that a native and enzymatically active V1 complex has been purified from the cytosol.
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PMID:Purification and properties of a cytosolic V1-ATPase. 870 48

Skeletal muscle is one of the major target organs for thyroid hormone. The muscles most commonly affected are those used during prolonged effort (slow-twitch muscles). One of the major clinical features is the shortening of the Achilles-tendon reflex time in hyperthyroidism and its prolongation in hypothyroidism. Most of the peripheral effects of the thyroid hormones can be ascribed to the action of triiodothyronine (T2), which is produced by de-iodination of thyroxine (T4) in liver and kidney. From the plasma, T3 is actively transported into skeletal muscle. The Ca2+ ATPase in skeletal muscle is responsible for removal of Ca2+ ions from the cytosol into the sarcoplasmic reticulum (SR) during relaxation, and the Na+, K+ ATPase in the plasma membrane is responsible for restoration of the membrane potential after excitation. The concentrations of Ca2+ ATPase and Na+, K+ ATPase in rat skeletal muscle have been shown to increase four- and 10-fold, respectively, in the transition from the hypothyroid to the hyperthyroid state. In humans, a linear correlation between the Na+, K+ ATPase concentration of skeletal muscle and the free T4 index was established. Significant effects of T3 on Ca2+ ATPase and Na+, K+ ATPase can be detected 24 h after a single injection. These effects are mediated by increased production of mRNA for the respective proteins, initiated by binding of T3 to nuclear receptors. Passive fluxes of Ca2+, Na+ and K+ also show a significant rise after T3 treatment. The increase in passive fluxes of Na+ and K+ can be detected before the rise in the concentration of Na+, K+ ATPase, suggesting that T3. In addition to its nuclear effects, may have a direct effect on the plasma membrane. Apart from their significance for muscle function in thyroid disease, the changes in Ca2+ ATPase and Na+, K+ ATPase will be important in other conditions where T3 and T4 levels show dramatic changes, i.e. during postnatal development, starvation and undernutrition, as well as in non-thyroidal illness (low-T3 syndrome).
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PMID:Effects of thyroid hormones on contractility and cation transport in skeletal muscle. 872 93

Aminophospholipid movements in the plasma membrane of higher eukaryotic cells seem to be regulated by an ATP-dependent, protein-mediated process. To examine whether similar mechanisms exist in yeast cells, we have analysed phosphatidylethanolamine (PtdEtn) distributions in Saccharomyces cerevisiae (A184D) cells under a variety of conditions, with trinitrobenzenesulfonic acid and fluorescamine as the external membrane probes. The levels of external PtdEtn in the intact cells were reduced to about 50% by pretreatment of the cells with inhibitors of mitochondrial ATP synthesis, ATPase inhibitors or protein-sulfhydryl-group-modifying reagents, or by depletion of the cells of ATP by metabolic starvation. The levels of external PtdEtn could be restored to normal by repletion of the energy-depleted cells with ATP. Furthermore, treatment of the energy-depleted cells with sulfhydryl-modifying reagents did not cause further reduction in the external PtdEtn levels but decreased the accessibility of PtdEtn to fluorescamine after restoration of the cellular ATP levels to normal in these cells. These results demonstrate an involvement of an ATP-dependent, protein-mediated process(es) in the regulation of the PtdEtn distribution across the plasma-membrane bilayer of yeast cells. The results are discussed with regard to possible models that can generate and maintain the transbilayer phospholipid asymmetry in the yeast plasma membrane.
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PMID:Transbilayer phosphatidylethanolamine movements in the yeast plasma membrane. Evidence for a protein-mediated, energy-dependent mechanism. 885 86

The unstable proteins Cdc6p and cdc18+ are essential and rate limiting for the initiation of DNA replication in Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively, and also participate in checkpoint controls that ensure DNA replication is completed before mitosis is initiated. We have identified Xenopus and human proteins closely related to Cdc6p/cdc18. The human protein, p62(cdc6), is encoded on chromosome 17q21.3 and includes putative cyclin-dependent kinase phosphorylation sites, destruction boxes, a nucleotide binding/ATPase domain, and a potential leucine zipper. Expression of p62(cdc6) mRNA and protein is suppressed in human diploid fibroblasts made quiescent by serum starvation, and peaks as cells reenter the cell cycle and replicate DNA following serum stimulation. Conservation of structure among proteins involved in initiation suggests that fundamental features of replication complexes are maintained in all eukaryotes.
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PMID:A human protein related to yeast Cdc6p. 899 Jan 75

Acidification inside vacuoles has been shown to play a key role in a number of physiologically important cellular events. We studied the role of vacuolar membrane H(+)-ATPase in the autophagic process of Saccharomyces cerevisiae. Mutants lacking VMA genes which encode their subunits of the vacuolar H(+)-ATPase accumulated autophagic bodies in vacuoles on starvation. vma mutants also had a defect in protein degradation induced by starvation. In vma mutants, the activities of vacuolar proteases were remarkably lower than those of the wild-type. Overexpression of vacuolar proteases did not overcome the defect in the disintegration of autophagic bodies in vma mutant, even the overexpressed proteinase A and proteinase B being substantially localized to the vacuolar compartment and undergoing proper proteolytic maturation. Our results showed that the acidification of vacuoles is not required for the formation and delivery of autophagosomes to vacuoles, but is essential for the disintegration of autophagic bodies.
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PMID:Acidification of vacuoles is required for autophagic degradation in the yeast, Saccharomyces cerevisiae. 908 9

The regulation of amino acid transport from the vacuolar reservoir into the cytoplasm has been studied in hyphal cells of Penicillium cyclopium. To avoid artifacts caused by the isolation of vacuoles, efflux was examined "in situ," i.e. in cells whose plasma membranes were permeabilized for micromolecules by a treatment with nystatin. The ATP-dependent proton gradient and amino acid transport activities at the vacuolar membrane remained intact under these conditions. Accumulation of amino acids in the vacuole proved to be the result of a dynamic equilibrium of active, ATP-dependent uptake and energy-independent efflux. The latter was strongly accelerated after the vacuolar amino acid content had surpassed a threshold level. Efflux of vacuolar amino acids was specifically controlled by extravacuolar adenylates: ATP, 5'-adenylyl imidodiphosphate (an ATPase-resistant ATP-analogue), ADP, or AMP caused a strong inhibition in the concentration range around 200 micromol/liter, whereas both lower and higher concentrations allowed significant efflux rates. Estimates of the cytosolic adenylates (which consisted mainly of ATP) were close to 2 mmol/liter in glucose-metabolizing cells, which concentration allowed maximum rates of both vacuolar uptake and efflux. During 24 h of carbon and nitrogen starvation, the adenylate level decreased toward the efflux-inhibiting region around 200 micromol/liter, whereas 3-4 d of carbon and nitrogen starvation caused a further decline of the adenylate content, leading again to efflux-permitting concentrations. Thus, the cytosolic adenylate pool appears to effectively control the availability of vacuolar amino acids for the cellular metabolism.
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PMID:Dynamic compartmentation of vacuolar amino acids in Penicillium cyclopium. Cytosolic adenylates act as a control signal for efflux into the cytosol. 918 83


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