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

Lifelong caloric restriction increases median and maximum life span and retards the aging process in many organ systems of rodents. Because the small intestine absorbs a reduced amount of nutrients each day, does lifelong caloric restriction induce adaptations in intestinal nutrient transport? We initially compared intestinal transport of sugars and amino acids between 24-mo-old mice allowed free access to food [ad libitum (AL)] and those provided a calorically restricted [40% less than ad libitum (CR)] diet since 3 mo of age. We found that CR mice had significantly greater transport rates for D-glucose, D-fructose, and several amino acids and had significantly lower villus heights. Total intestinal absorptive capacities for D-glucose, D-fructose, and L-proline were each 40-50% greater in CR mice; absorptive capacity normalized to metabolic mass (body weight 0.75) was approximately 80% greater in CR mice. Comparison of uptakes in aged AL and CR mice with previously published results in young AL mice suggests that caloric restriction delays age-related decreases in nutrient transport. In contrast to published studies in hibernation and starvation, chronic caloric restriction enhances not only uptake per milligram but also uptake per centimeter. We then switched 24-mo-old AL mice to a calorie-restricted diet for 1 mo and found that short-term caloric restriction has no effect on intestinal nutrient transport, intestinal mass, and total absorptive capacity. Thus chronic but not short-term caloric restriction increases intestinal nutrient transport rates in aged mice, and the main mechanism underlying these increases is enhanced transport rates per unit intestinal tissue weight.
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PMID:Adaptations of intestinal nutrient transport to chronic caloric restriction in mice. 876 Jan 23

Starvation for nitrogen in the absence of a fermentable carbon source causes diploid Saccharomyces cerevisiae cells to leave vegetative growth, enter meiosis, and sporulare; the former nutritional condition also induces expression of the YVH1 gene that encodes a protein phosphatase. This correlation prompted us to determine whether the Yvh1p phosphatase was a participant in the network that controls the onset of meiosis and sporulation. We found that expression of the IME2 gene, encoding a protein kinase homologue required for meiosis- and sporulation-specific gene expression, is decreased in a yvh1 disrupted strain. We also observed a decrease, albeit a smaller one, in the expression of IME1 which encodes an activator protein required for IME2 expression. Under identical experimental conditions, expression of the MCKI and IME4 genes (which promote sporulation but do not require Ime1p for expression) was not affected. These results demonstrate the specificity of the yvh1 disruption phenotype. They suggest that decreased steady-state levels of IME1 and IME2 mRNA were not merely the result of non-specific adverse affects on nucleic acid metabolism caused by the yvh1 disruption. Sporulation of a homozygous yvh1 disruption mutant was delayed and less efficient overall compared to an isogenic wild-type strain, a result which correlates with decreased IME1 and IME2 gene expression. We also observed that expression of the PTP2 tyrosine phosphatase gene (a negative regulator of the osmosensing MAP kinase cascade), but not the PTP1 gene (also encoding a tyrosine phosphatase) was induced by nitrogen-starvation. Although disruption of PTP2 alone did not demonstrably affect sporulation or IME2 gene expression, sporulation was decreased more in a yvh1, ptp2 double mutant than in a yvh1 single mutant; it was nearly abolished in the double mutant. These data suggest that the YVH1 and PTP2 encoded phosphatases likely participate in the control network regulating meiosis and sporulation. Expression of YVH1 and PTP2 was not affected by nitrogen source quality (asparagine compared to proline) suggesting that nitrogen starvation-induced YVH1 and PTP2 expression and sensitivity to nitrogen catabolite repression are on two different branches of the nitrogen regulatory network.
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PMID:The S. cerevisiae nitrogen starvation-induced Yvh1p and Ptp2p phosphatases play a role in control of sporulation. 889 80

The phenomenon of starvation-induced apoptosis was studied in cultures of a mouse B lymphocyte hybridoma. In a continuous culture the limitation of nutrients was modelled by dilution of a protein-free medium with saline to 15%. Surprisingly, the hybridoma clone did not die out under extreme starvation conditions. A steady state was established in which the cells continued to grow at very low viable cell concentration, concomitantly with an enhanced rate of apoptotic death. Suppression of the death rate, and increase of steady-state viable cell concentration, could be achieved by additions of L-alanine, L-asparagine or L-glutamine, but not by addition of L-phenylalanine. This specificity pattern is in agreement with previous screening experiments that have identified a set of apoptosis-preventing amino acids (glycine, L-alanine, L-serine, L-threonine, L-proline, L-asparagine, L-glutamine, L-histidine). The analysis of amino acid consumption and production showed a consistent production of alanine and serine both in standard medium and in diluted media. When alanine was added at a final concentration of 2 mM to media diluted either to 40 or 20%, apoptosis was partly suppressed. A limited production of alanine was observed also in alanine-enriched diluted media. It is concluded that the apoptosis-preventing amino acids act as signal molecules, besides their nutritive function, and that the signal has a character of a survival factor. The observed phenomena are interpreted in terms of a survival-control mechanism that regulates the viable cell number of a lymphocyte clone in an adequate proportion with the level of available nutrients.
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PMID:Protection of B lymphocyte hybridoma against starvation-induced apoptosis: survival-signal role of some amino acids. 890 9

In Aspergillus nidulans a highly specific L-proline transporter is encoded by the prnB gene which is tightly linked to all other genes involved in proline catabolism. In mycelia, the expression of the prn structural genes is finely co-regulated in response to proline induction and nitrogen/carbon catabolite repression. In this study we establish that prnB expression is also activated during germination of conidiospores. This activation persists until the development of 6 h-old mycelia and it is independent of proline induction mediated by the pathway-specific prnA gene product. We then show that, in mycelia, prnB transcription is activated in response to proline or histidine starvation. This process has two components: a prnA-dependent and a prnA-independent component. A cis-acting element that conforms to the consensus target of the GCN4/CPC1 transcriptional activators mediating amino acid biosynthesis activation in other fungi is involved in the activation of prnB transcription in response to amino acid starvation. We also show that the stimulation of prnB expression in germinating conidiospores is not due exclusively to transient internal amino acid starvation occurring during the transition from conidiospore to mycelium. This is the first report that an amino acid transporter gene is upregulated during development and in response to amino acid starvation and specific amino acid induction.
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PMID:The gene encoding the major proline transporter of Aspergillus nidulans is upregulated during conidiospore germination and in response to proline induction and amino acid starvation. 914 Sep 69

The production of some extracellular enzymes is known to be negatively affected by readily metabolized nitrogen sources such as NH4+ although there is no consensus regarding the involved mechanisms. Asparaginase II is a periplasmic enzyme of Saccharomyces cerevisiae encoded by the ASP3 gene. The enzyme activity is not found in cells grown in either ammonia, glutamine, or glutamate, but it is found in cells that have been subjected to nitrogen starvation or have been grown on a poor source of nitrogen such as proline. In this report it is shown that the formation of this enzyme is dependent upon the functional GLN3 gene and that the response to nitrogen availability is under the control of the URE2 gene product. In this respect the expression of ASP3 is similar to the system that regulates the GLN1, GDH2, GAP1, and PUT4 genes that codes for glutamine synthetase, NAD-linked glutamate dehydrogenase, general amino-acid permease, and high affinity proline permease, respectively.
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PMID:Asparaginase II of Saccharomyces cerevisiae. GLN3/URE2 regulation of a periplasmic enzyme. 917 Feb 45

The regulation of the high affinity cationic amino acid transporter Cat-1 in Fao rat hepatoma cells by amino acid availability has been studied. Cat-1 mRNA level increased (3-fold) in 4 h in response to amino acid starvation and remained high for at least 24 h. This induction was independent of the presence of serum in the media and transcription and protein synthesis were required for induction to occur. When Fao cells were shifted from amino acid-depleted media to amino acid-fed media, the levels of the induced cat-1 mRNA returned to the basal level. In amino acid-fed cells, accumulation of cat-1 mRNA was dependent on protein synthesis, indicating that a labile protein is required to sustain cat-1 mRNA level. No change in the transcription rate of the cat-1 gene during amino acid starvation was observed, indicating that cat-1 is regulated at a post-transcriptional step. System y+ mediated transport of arginine was reduced by 50% in 1 h and by 70% in 24 h after amino acid starvation. However, when 24-h amino acid-starved Fao cells were preloaded with 2 mM lysine or arginine for 1 h prior to the transport assays, arginine uptake was trans-stimulated by 5-fold. This stimulation was specific for cationic amino acids, since alanine, proline, or leucine had no effect. These data lead to the hypothesis that amino acid starvation results in an increased cat-1 mRNA level to support synthesis of additional Cat-1 protein. The following lines of evidence support the hypothesis: (i) the use of inhibitors of protein synthesis in starved cells inhibits the trans-zero transport of arginine; (ii) cells starved for 1-24 h exhibited an increase of trans-stimulated arginine transport activity for the first 6 h and had no loss of activity at 24 h, suggesting that constant replenishment of the transporter protein occurs; (iii) immunofluorescent staining of 24-h fed and starved cells for cat-1 showed similar cell surface distribution; (iv) new protein synthesis is not required for trans-stimulation of arginine transport upon refeeding of 24-h starved cells. We conclude that the increased level of cat-1 mRNA in response to amino acid starvation support the synthesis of Cat-1 protein during starvation and increased amino acid transport upon substrate presentation. Therefore, the cat-1 mRNA content is regulated by a derepression/repression mechanism in response to amino acid availability. We propose that the amino acid-signal transduction pathway consists of a series of steps which include the post-transcriptional regulation of amino acid transporter genes.
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PMID:Adaptive regulation of the cationic amino acid transporter-1 (Cat-1) in Fao cells. 924 63

Changes in surface area of microvilli, fluidity of brush border membrane and transport of L-amino acids through intestinal epithelial cells were studied in wellfed and starved (2,4 and 6 days) rats. The surface area of microvilli per unit area of intestinal epithelial cells increased during starvation. Studies with fluoroprobes - pyrene, 1-anilinonaphthalene-8-sulphonate and 1,6-diphenyl-1,3,5-hexatriene, showed increased fluidity of brush border membrane on progressive starvation. Transport of five amino acids representing five different transport systems was studied during starvation in everted intestinal sleeves. Transport of L-proline, glycine and L-glutamic acid which represent imino, glycine and acidic systems respectively increased significantly in Na+-dependent pathway whereas transport of L-lysine representing basic system increased significantly in Na+-independent pathway during starvation.
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PMID:Changes in structural and functional properties of rat intestinal brush border membrane during starvation. 941 61

Sphingoid long chain bases have many effects on cells including inhibition or stimulation of growth. The physiological significance of these effects is unknown in most cases. To begin to understand how these compounds inhibit growth, we have studied Saccharomyces cerevisiae cells. Growth of tryptophan (Trp-) auxotrophs was more strongly inhibited by phytosphingosine (PHS) than was growth of Trp+ strains, suggesting that PHS diminishes tryptophan uptake and starves cells for this amino acid. This hypothesis is supported by data showing that growth inhibition is relieved by increasing concentrations of tryptophan in the culture medium and by multiple copies of the TAT2 gene, encoding a high affinity tryptophan transporter. Measurement of tryptophan uptake shows that it is inhibited by PHS. Finally, PHS treatment induces the general control response, indicating starvation for amino acids. Multiple copies of TAT2 do not protect cells against two other cationic lipids, stearylamine, and sphingosine, indicating that the effect of PHS on tryptophan utilization is specific. Other data demonstrate that PHS reduces uptake of leucine, histidine, and proline by specific transporters. Our data suggest that PHS targets proteins in the amino acid transporter family but not other distantly related membrane transporters, including those necessary for uptake of adenine and uracil.
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PMID:Inhibition of amino acid transport by sphingoid long chain bases in Saccharomyces cerevisiae. 944 92

The mycobacillin-sensitive Aspergillus niger strain G3Br and resistant mutants of it did not show any differences in their total lipid content, although the amounts of phospholipids and sterols, particularly phosphatidylcholine and cholesterol, were lower in resistant cells. Mycobacillin resistance was accompanied by an increase in the phase-transition temperature of plasma membrane preparations. When exposed to mycobacillin, resistant and sensitive cells did not differ qualitatively with respect to most released materials (lysine, proline, Pi, Na+, K+, Ca2+); however, the release of ATP was completely inhibited in resistant cells unless they were exposed to concentrations of mycobacillin exceeding their respective MIC value. Resistant cells, under steady-state conditions, displayed greater uptake and release of the same specific materials--except ATP--as sensitive cells did under similar conditions. Thus release and uptake of those materials except ATP are not implicated in the mode of action of mycobacillin. The inhibiting action of mycobacillin (at concentrations higher than the MIC) on sensitive or resistant cells was completely antagonized by ATP (which did not form any complex with mycobacillin) but not by any of the releasable components, either alone or in combination. This observation, coupled with the authors' recent findings on ATP release, indicates that the fungistatic action of mycobacillin is due to excessive ATP release, leading to energy starvation. Interestingly, ATP release during the first 2 h of incubation with mycobacillin was minimal, but increased to over 96% during the next 48 h. Release and uptake of ATP via liposomes, prepared with lipid and protein isolated from membranes of the mycobacillin-sensitive parent and resistant mutants, showed that mycobacillin action could be inhibited either by resistant protein or by resistant lipid. The mycobacillin target appears to be a lipid-protein site on the membrane of sensitive A. niger G3Br.
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PMID:Use of resistant mutants to characterize the target of mycobacillin in Aspergillus niger membranes. 957 85

Cyclophilin (the product of the ppiB gene) and the trigger factor (the product of the tig gene) are the only cytosolic peptidyl-prolyl cis-trans isomerases that are known in Bacillus subtilis. Both enzymes catalyze the in vitro refolding of ribonuclease T1, a reaction that is limited in rate by a prolyl cis/trans isomerization. The efficiency of cyclophilin as a folding catalyst is only modest with a kcat/KM value of 3.8 x 10(4) M-1 s-1, but the trigger factor shows an almost 40-fold higher specific activity with a kcat/KM value of 1.4 x 10(6) M-1 s-1. This high catalytic activity originates from the tight binding to the protein substrate as reflected in both the low KM value of 0.5 microM and in the strong inhibition of the trigger factor by unfolded proteins. By use of a protein-folding assay, the concentrations of cyclophilin and the trigger factor in the cytosol of B. subtilis could be determined as 26 and 35 microM, respectively. Together they account for the entire folding activity that is detectable in crude extracts of wild-type B. subtilis cells. The genes encoding cyclophilin and the trigger factor in the B. subtilis chromosome were disrupted individually and simultaneously. Even in combination, these disruptions had no effect on cell viability in rich medium or under several stress conditions, such as heat, osmotic, or oxidative stress. However, in poor medium and, in particular, in the absence of amino acids, the growth of the double mutant strain was strongly decelerated, indicating that the prolyl isomerases become essential for growth under starvation conditions. It is not yet known whether this function relates to the catalysis of the proline-limited folding of essential proteins.
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PMID:Cyclophilin and trigger factor from Bacillus subtilis catalyze in vitro protein folding and are necessary for viability under starvation conditions. 974 46


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