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

We have studied the regulation of expression of the asparagine synthetase (AS) gene in ts11 cells, a mutant of BHK hamster cells which encodes a temperature-sensitive AS and therefore does not produce endogenous asparagine at 39.5 degrees C. Incubation of ts11 cells at the nonpermissive temperature drastically increases the level of AS mRNA, and the stimulation of AS mRNA expression is effectively suppressed by the addition of asparagine to the medium. We show here that regulation of AS gene expression involves cis-acting elements which are contained in the mRNA as well as in the 5' genomic region. When a plasmid containing the human AS cDNA under the control of the human AS promoter region was stably transfected into ts11 cells, the expression of human AS RNAs was regulated as that of the endogenous hamster transcripts, indicating that this construct contained all cis elements necessary for regulation. Expression of the AS cDNA in ts11 cells under the control of a constitutive foreign promoter was also regulated by the concentration of asparagine, and this regulation required translation. When we introduced by mutagenesis a number of stop codons in the AS cDNA, the mutant mRNAs with short open reading frames were expressed at low levels that were not increased by asparagine deprivation. Inhibition of protein and RNA synthesis also prevented down-regulation of AS mRNA levels by high concentrations of asparagine. In a parallel series of experiments, we showed that an AS DNA fragment including the promoter and first exon can also regulate RNA expression in response to asparagine concentration. Furthermore, similar increases in the levels of AS RNAs are produced not only by asparagine deprivation in ts11 cells but also by deprivation of human and wild-type BHK cells of leucine, isoleucine, or glutamine. Thus, regulation of AS gene expression is a response to amino acid starvation through mechanisms which appear to involve both changes in RNA stability and change in the rates of transcription initiation or elongation.
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PMID:Regulation of asparagine synthetase gene expression by amino acid starvation. 168 98

The activity of asparagine synthetase decreased almost 50% during dexamethasone-induced mouse myeloid leukemia M1 cell differentiation. This enzyme activity also declined significantly during differentiation of the human myelogenous leukemic cell lines, HL-60 and U-937, induced by either macrophage culture supernatant or retinoic acid. The decline of asparagine synthetase activity closely paralleled the expression of various maturation markers, but could also be induced by serum starvation. These results suggest that asparagine synthetase or L-asparagine has some biological function in growth regulation of these leukemia cell lines.
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PMID:Decrease in asparagine synthetase activity during cell differentiation of mouse and human leukemia cell lines. 197 72

We have used a Chinese hamster ovary cell line deficient in N-acetylglucosaminyltransferase 1 activity (Lec1) to study the effects of altered asparagine-linked oligosaccharides on the structure, biosynthesis, and function of glucose transporter protein. Immunoblots of membranes of Lec1 cells show a glucose transporter protein of Mr 40,000, whereas membranes of wild-type (WT) cells contain a broadly migrating Mr 55,000 form similar to that observed in several other mammalian tissues. The total content of immunoreactive glucose transporters in Lec1 cells is 3.5-fold greater than that of WT cells. Digestion with endoglycosidases, treatment with inhibitors of glycosylation, and interactions with agarose-bound lectins demonstrate that glucose transporters of both cell lines derive from a similar Mr 38,000 core polypeptide and that both contain asparagine-linked oligosaccharide. Transporters in Lec1 cells contain primarily "undecorated" but "trimmed" mannose-type asparagine-linked oligosaccharides, while the protein in WT cells contains a mixture of "decorated" and "trimmed" asparagine-linked oligosaccharides. Biosynthetic and turnover studies demonstrate that Lec1 cells, in contrast to WT cells, are unable fully to process the core asparagine-linked oligosaccharides of maturing glucose transporters. When radiolabeled in methionine-deficient medium both Lec1 and WT cells show similar rates of synthesis and turnover of glucose transporter proteins. It should be noted, however, that starvation for a critical amino acid may alter the ability of the cell to synthesize or degrade proteins. The abilities of Lec1 and WT cells to transport hexoses and to interact with the inhibitor cytochalasin B are very similar. The results indicate that, although altered asparagine-linked glycosylation can affect the content and biogenesis of glucose transporters, these changes do not greatly modify cellular hexose uptake. The possibility that alterations in asparagine-linked glycosylation may change the cell surface localization or acquisition of a "functional conformation" of the glucose transporter is also suggested.
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PMID:Structure, biosynthesis, and function of the hexose transporter in Chinese hamster ovary cells deficient in N-acetylglucosaminyltransferase 1 activity. 297 Apr 67

During asparagine starvation the frequency of lysine for asparagine substitutions increases to levels that enable one to isolate and sequence mistranslated protein. We have used site-directed mutagenesis to construct a series of derivatives of the gene encoding the coat protein of the bacteriophage MS2. The mutant set constructed has either AAU or AAC as codon three in the gene with each possible adjoining 3' base. Lysine incorporation in coat protein encoded by these genes shows that AAU is misread from 4- to 9-fold more frequently than AAC with any 3' context. Although in some cases context effects of approximately 2-fold were noted, there seems to be no simple hypothesis to explain them.
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PMID:Missense misreading of asparagine codons as a function of codon identity and context. 311 58

Concentrations of free amino acids were measured in human milk and arterial blood from lactating women after an overnight fast or after a controlled breakfast. The concentrations of many free amino acids in milk (except L-tyrosine, L-aspartate, L-asparagine, L-glutamate and L-glutamine) were lower after an overnight fast than after breakfast. Similarly, the arterial concentrations of amino acids were lower except for L-asparagine, L-alanine, L-tyrosine and L-phenylalanine. Net uptake of amino acids by the mammary gland of the lactating rat was significantly lower after starvation for 6 or 24 h than in the fed state because the arteriovenous differences of amino acids and the blood flow were significantly lowered. Starvation produced a significant decrease of 2-amino-[1-14C]isobutyric acid uptake by isolated acini from lactating rat. These results show that short-term starvation decreases the amino acid supply and transport in mammary gland as well as the free amino acid concentration in milk.
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PMID:Effect of fasting on amino acid metabolism by lactating mammary gland: studies in women and rats. 357 66

Branched-chain amino acid metabolism in skeletal muscle promotes the production of alanine, an important precursor in hepatic gluconeogenesis. There is controversy concerning the origin of the carbon skeleton of alanine produced in muscle, specifically whether it is derived from carbohydrate via glycolysis (the glucose-alanine cycle) or from amino acid precursors (viz. glutamate, valine, isoleucine, methionine, aspartate, asparagine) via a pathway involving phosphoenolpyruvate (PEP) carboxykinase and pyruvate kinase, or NADP-malate dehydrogenase (malic enzyme). The relevant literature is reviewed and it is concluded that neogenic flux from amino acids is unlikely to be of major quantitative importance for provision of the carbon skeleton of alanine either in vitro or in vivo. Evidence is presented that branched-chain amino acid oxidation in muscle is incomplete and that the branched-chain 2-oxo acids and the products of their partial oxidation (including glutamine) are released. The role of these metabolites is discussed in the context of fuel homeostasis in starvation.
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PMID:Alanine and inter-organ relationships in branched-chain amino and 2-oxo acid metabolism. Review. 393 2

1. The activity of l-asparaginase was very low in the liver of newborn rats and mice, and increased within a few days of birth. 2. In rats, but not in mice, the enzyme activity was higher in females than in males, was enhanced by administration of oestradiol, and was decreased by gonadectomy. 3. The enzyme activity decreased in mice starved or fed on a low-protein diet; in rats it was enhanced by starvation, by feeding them on a high-protein diet, or by administration of l-asparagine. 4. The asparaginase activity was decreased in regenerating liver, and was almost absent in the Morris hepatoma 5123.
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PMID:The regulation of L-asparaginase activity in rats and mice. Effects of normal and malignant growth, of sex and of dietary changes. 431 Oct 65

Albumin synthesis was measured in the isolated perfused rat liver by using the livers of both well-fed and starved rats. Starvation markedly decreased albumin synthesis. The livers from starved rats were unable to increase synthesis rates after the addition to the perfusates of single amino acids or the addition of both glucagon and tryptophan. Arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine, added together to ten times their normal peripheral blood concentrations, restored synthesis rates to normal. The plasma aminogram (i.e. the relative concentrations, of amino acids) was altered by depriving rats of protein for 48h. The use of blood from the deprived rats as perfusate, instead of normal blood, decreased albumin synthesis rates significantly by livers obtained from well-fed rats. The addition of single amino acids, including the non-metabolizable amino acid, alpha-aminoisobutyric acid, to the above mixture increased albumin synthesis rates to normal values. It is concluded that amino acids play an important role in the control of albumin synthesis and that more than one mechanism is probably involved.
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PMID:The effects of amino acids on albumin synthesis by the isolated perfused rat liver. 465 17

The methylation of nucleic acids has been investigated during the cell cycle of an asparagine dependent strain of transformed fibroblasts (BHK 21 HS 5). The synchrony was carried out by a partial asparagine starvation of cells for 24 hours. The amino acid supply induced all cells to enter synchronously the G1 phase. Methylation and DNA synthesis were respectively measured by pulsed [methyl-14C] methionine and [methyl-3H] thymidine incorporation. DNA methylation followed a biphasic pattern with maximal methyl incorporations during both S phase and mitosis. A partial desynchronisation induced the S phase of the second cycle to proceed before all the cells have achieved their division. Hydroxyurea was used in order to inhibit the DNA synthesis of cells entering the second cell cycle, which might interfer with the mitosis of the first one. The inhibitor was added either at the first beginning of cell division or during all the G1 phase. In both conditions it suppressed 3H thymidine incorporation of the second cycle. However, mitosis took place and methylations occurred as in previous experiments. The DNA methylation of the mitotic phase in the first cell cycle could thus be dissociated from the classical post-synthetic DNA maturation and did not correspond to any DNA methylation appearing in the course of the second cell cycle.
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PMID:Nucleic acids methylation of synchronized BHK 21 HS 5 fibroblasts during the mitotic phase. 615 63

Basal-level misreading of asparagine codons was examined in a number of Escherichia coli strains. Lysine substitutions were measured by quantitating the amount of charge heterogeneity in MS2 coat protein. In most strains the heterogeneity was consistent with misreading of AAU codons at a frequency of 3-6 X 10(-3). Strains with streptomycin resistance mutations (rpsL) have reduced levels of misreading. There is no significant difference in the frequency of basal-level errors in stringent (relA+) and relaxed (relA) strains, even during starvation for amino acids unrelated to the substitution being studied.
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PMID:Control of basal-level codon misreading in Escherichia coli. 637 72


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