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

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

Starvation, glucagon and cyclic AMP inhibit, and refeeding starved animals and insulin or IGF-I plus triiodothyronine stimulate accumulation of FAS and its mRNA in liver; transcription is the primary regulated step. In the uropygial gland, differentiation of basal cells into mature sebocytes is accompanied by the accumulation of large amounts of FAS and its mRNA. By analogy with liver, transcription is likely to be the regulated step, but direct experimental evidence for this hypothesis is lacking. FAS mRNA is a unique gene and is probably more than 100 kb in length. The FAS gene of goose and duck is transcribed into two mature mRNAs of about 10,800 and 12,200 nucleotides. The 3'-untranslated regions of the FAS mRNAs contain an unusual polypyrimidine tract which, at the mRNA level at least, appears unrelated to regulation of gene expression. Polypyrimidine tracts similar in sequence to that in the FAS gene are found in about 20 different parts of the genome. All of the fragments which contain these tracts are hypermethylated. The next stage of this investigation will involve identification of cis-acting sequence elements in the FAS gene which specify responses to diet, hormones and tissue-specific regulatory factors. Isolation and characterization of the 5'-ends of the cDNA and the gene are underway.
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PMID:Structure and regulation of the avian gene for fatty acid synthase. 259 Mar 94

The degradation of intracellular protein and other cytoplasmic macromolecules in liver is an ongoing process that regulates cytoplasmic mass and provides amino acids for energy and other metabolic uses early in starvation. Cellular proteins are conveniently divided into two general classes according to readily discernable differences in average rates of turnover. A short-lived class, having a half-life of approximately 10 min, comprises about 0.6% of total protein. Its degradation is not physiologically controlled, and the mechanism is probably nonlysosomal in nature. The second or long-lived group, with an average half-life 250 times greater, constitutes more than 99% of the cell's protein. By contrast, its breakdown is strongly regulated, and the site of catabolism is believed to be the vacuolar-lysosomal system. Cytoplasmic sequestration by lysosomes can be divided into two categories; macro- and microautophagy. The first is induced by amino acid and/or insulin deprivation. Amino acids are considered to be primary regulators, since they can control this process over the full range of induced proteolysis in the absence of hormones. Glucagon, cyclic AMP, and beta-agonists also stimulate macroautophagy in hepatocytes but have opposite effects in myocytes. Micrautophagy differs from the former in that the cytoplasmic "bite" is smaller and the uptake process is not acutely regulated. However, the latter does decrease during starvation in parallel with basal proteolysis, effects that might be linked to the loss of endoplasmic reticulum. The primary control of macroautophagy is accomplished through a small group of direct regulators (Leu, Tyr/Phe, Gln, Pro, Met, His, and Trp) and a specific coregulatory action of alanine. As a group, regulatory amino acids produce direct inhibitory responses in the perfused rat liver that are identical to those of the complete amino acid mixture at 0.5x and 4x (times) normal plasma concentrations. However, they lose effectiveness almost completely within a narrow zone centered at normal levels, a loss that can be abolished by the addition of alanine at its normal plasma concentration (0.5 mM). At this level, alanine does not inhibit directly. Interestingly, this zonal loss is also eliminated by insulin. Glucagon, though, specifically blocks the initial inhibition evoked by 0.5x amino acid mixtures and thus induces maximal rates of protein degradation at normal amino acid concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism and regulation of protein degradation in liver. 264 36

Mutations in the SRA1 or SRA3 gene eliminate the requirement for either RAS gene (RAS1 or RAS2) in Saccharomyces cerevisiae. We cloned SRA1 and SRA3 and determined their DNA sequences. SRA1 encodes the regulatory subunit of the cyclic AMP (cAMP)-dependent protein kinase and therefore is identical to REG1 and BCY1. This gene is not essential, but its deletion confers many traits: reduction of glycogen accumulation, temperature sensitivity, reduced growth rate on maltose and sucrose, inability to grow on galactose and nonfermentable carbon sources, and nitrogen starvation intolerance. SRA3 is homologous to protein kinases that phosphorylate serine and threonine and likely encodes the catalytic subunit of the cAMP-dependent protein kinase. The wild-type SRA3 gene either triplicated in the chromosome or on episomal, low-copy plasmids behaves like spontaneous dominant SRA3 mutations by suppressing ras2-530 (RAS2::LEU2 disruption), cdc25, and cdc35 mutations. These findings indicate that the yeast RAS genes are dispensable if there is constitutive cAMP-dependent protein kinase activity.
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PMID:Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase. 282

sra5 mutations in Saccharomyces cerevisiae were previously shown to suppress the inefficient growth of ras2 strains on nonfermentable carbon sources and to result in deficient low-Km cyclic AMP (cAMP) phosphodiesterase activity. We have cloned SRA5 by complementation. It maps to the right arm of chromosome XV, tightly linked to PRT1, and its sequence matches the sequence of PDE2, encoding the low-Km cAMP phosphodiesterase. Disruptions of SRA5 allowed ras1 ras2 strains to grow either on rich media supplemented with cAMP or on minimal media without exogenous cAMP. sra5 strains failed to survive prolonged nitrogen starvation in the presence of exogenous cAMP.
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PMID:SRA5 encodes the low-Km cyclic AMP phosphodiesterase of Saccharomyces cerevisiae. 282 10

Changes in plasma glucose, hepatic cyclic AMP, glycogen and fructose 2,6-bisphosphate (F-2,6-P2), and liver 6-phosphofructo-2-kinase (6-PF-2kinase), fructose 2,6-bisphosphatase (F-2,6-P2ase) and phosphoenolpyruvate carboxykinase (PEPCK) activities were examined in rats fed a low protein, high carbohydrate (HC) diet during 3 d of either starvation or feeding a high protein, carbohydrate-free (HP) diet. Under both HP feeding or starvation, liver cyclic AMP increased after 1 d and remained constant thereafter. Whereas plasma glucose was low during starvation, it was unaffected by HP feeding. In both experimental groups, liver glycogen fell after 1 d; thereafter it remained low on starvation, but increased progressively on HP diet reaching 70% of the HC-fed rats value on day 3. Under both experimental conditions, F-2,6-P2 fell 85% after day 1 and was unchanged thereafter. One day after the start of starvation or consumption of the HP diet, 6-PF-2kinase decreased, F-2,6-P2ase increased and 6-PF-2kinase/F-2,6-P2ase ratio decreased, but changes were significantly more important with the HP diet than with starvation. PEPCK activity increased in both experimental conditions, but the increase was greater on the HP diet than on starvation. These findings suggest that during the first 3 d the adaptative response of hepatic gluconeogenesis is higher with a HP diet than upon starvation.
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PMID:Changes in rat hepatic fructose 2,6-bisphosphate and 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase activity during three days of consumption of a high protein diet or starvation. 282 29

Of the 30 carbon starvation proteins whose induction has been previously shown to be important for starvation survival of Escherichia coli, two-thirds were not induced in cya or crp deletion mutants of E. coli at the onset of carbon starvation. The rest were induced, although not necessarily with the same temporal pattern as exhibited in the wild type. The starvation proteins that were homologous to previously identified heat shock proteins belonged to the latter class and were hyperinduced in delta cya or delta crp mutants during starvation. Most of the cyclic AMP-dependent proteins were synthesized in the delta cya mutant if exogenous cyclic AMP was added at the onset of starvation. Furthermore, beta-galactosidase induction of several carbon starvation response gene fusions occurred only in a cya+ genetic background. Thus, two-thirds of the carbon starvation proteins of E. coli require cyclic AMP and its receptor protein for induction; the rest do not. The former class evidently has no role in starvation survival, since delta cya or delta crp mutants of either E. coli or Salmonella typhimurium survived starvation as well as their wild-type parents did. The latter class, therefore, is likely to have a direct role in starvation survival. This possibility is strengthened by the finding that nearly all of the cya- and crp-independent proteins were also induced during nitrogen starvation and, as shown previously, during phosphate starvation. Proteins whose synthesis is independent of cya- and crp control are referred to as Pex (postexponential).
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PMID:Differential regulation by cyclic AMP of starvation protein synthesis in Escherichia coli. 284 91

The growth of transformed mouse fibroblasts (3T6 cells) in medium containing 5% fetal bovine serum was inhibited after treatment with concentrations greater than 50 microM ATP, ADP, or AMP. Adenosine, the common catabolite of the nucleotides, had no effect on cell growth at concentrations below 1 mM. However, the following results indicate that the toxicity of ATP, ADP, and AMP is mediated by serum- and cell-associated hydrolysis of the nucleotides to adenosine. 1) ADP and AMP, but not ATP, were toxic to 3T6 cells grown in serum-free medium or medium in which phosphohydrolase activity of serum was inactivated. Under these conditions, the cells exhibited cell-associated ADPase and 5'-nucleotidase activity, but little ecto-ATPase activity. 2) Inhibition of adenosine transport in 3T6 cells by dipyridamole or S-(p-nitrobenzyl)-6-thioinosine prevented the toxicity of ATP in serum-containing medium and of ADP and AMP in serum-free medium. 3) A 16-24-h exposure to 125 microM AMP or ATP was needed to inhibit cell growth under conditions where serum- and cell-associated hydrolysis of the nucleotides generated adenosine in the medium continuously over the same time period. In contrast, 125 microM adenosine was completely degraded to inosine and hypoxanthine within 8-10 h. Furthermore, multiple doses of adenosine added to the cells at regular intervals over a 16-h period were significantly more toxic than an equivalent amount of adenosine added in one dose. Treatment of 3T6 cells with AMP elevated intracellular ATP and ADP levels and reduced intracellular UTP levels, effects which were inhibited by extracellular uridine. Uridine also prevented growth inhibition by ATP, ADP, and AMP. These and other results indicate that serum- and cell-associated hydrolysis of adenine nucleotides to adenosine suppresses growth by adenosine-dependent pyrimidine starvation.
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PMID:Growth inhibition of transformed mouse fibroblasts by adenine nucleotides occurs via generation of extracellular adenosine. 284 30

1. The fluctuations in rat hepatocyte volume and protein content in response to dietary perturbations (starvation, protein restriction, refeeding) were accompanied by corresponding fluctuations in the amount of the regulatory (R) and catalytic (C) subunits of cyclic AMP-dependent protein kinase. Thus the intracellular concentration of this key enzyme was adjusted to be near constant. 2. The adjustment of cellular R was accomplished almost exclusively by regulating cytosolic RI (R subunit of type I kinase). The preferential down-regulation of cytosolic RI in response to starvation/protein restriction indicates that particulate RI and cytosolic as well as particulate RII are more resistant to breakdown during general catabolism in the hepatocyte. 3. The diet-induced fluctuations of kinase subunits were uniformly distributed in all populations of parenchymatous hepatocytes, regardless of their size and density. It is thus possible to isolate hepatocytes with uniformly altered RI/RII ratio from livers of rats with different feeding regimens. 4. The binding of endogenous cyclic AMP to RI and RII was similar in livers with high RI/RII ratio (fed rats) and low RI/RII ratio (fasted rats) as well as in hepatocytes isolated from fasted rats. Under the conditions of the experiment (short-term stimulation by glucagon), therefore, neither the dietary state nor the RI/RII ratio seemed to affect the apparent affinity of the isoreceptors for cyclic AMP. However, RI appeared to show a slightly higher co-operativity of intracellular cyclic AMP binding than did RII in all states.
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PMID:The amounts of rat liver cyclic AMP-dependent protein kinase I and II are differentially regulated by diet. 285 90


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