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)

This study illustrates the specific immune response of chronically starved, undernourished adults after inoculation of live smallpox vaccine. It produced no adverse effect, and major vaccinial reaction was observed in all. 63% of undernourished individuals showed a fourfold or greater rise of the neutralizing antibody titre. In contrast, only 9% of normal healthy subjects could show similar response. However, the prevaccination titre was much lower in the undernourished group than in the control group, and the postvaccination titre also remained persistently lower in the former than in the latter group. Furthermore, whereas the specific humoral antibody response in the undernourished subjects was partially adequate, the development of specific cellular immunity against vaccinia was remarkably poor, indicating that smallpox vaccination in these subjects might be less effective against variola infection. This observed profound effect of chronic starvation and severe undernutrition on the immune apparatus was possibly multifactorial, protein depletion being the most important factor, as proved by the significantly low serum albumin level. The significantly low peripheral blood lymphocyte count and spectacular unresponsiveness to many antigens in these individuals suggested profound depression of the thymolymphatic system. Further, the significantly low level of neutralizing antibody in the malnourished subjects suggested that the formation of this protective antibody might necessitate the cooperation of T lymphocytes.
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PMID:Undernutrition and immunity: smallpox vaccination in chronically starved, undernourished subjects and its immunologic evaluation. 19 73

A phosphatase related to the vaccinia virus VH1 phosphatase has been cloned from Saccharomyces cerevisiae. The yeast phosphatase is related to the Schizosaccharomyces pombe cdc25 gene product and to a protein encoded by a mammalian open reading frame known as 3CH134, which is an immediate early gene responding to serum stimulation. The phosphatase activity of the yeast gene product appears to be restricted to the hydrolysis of phosphotyrosine-containing substrates, whereas the vaccinia phosphatase hydrolyzes both phosphoserine- and phosphotyrosine-containing substrates. The mRNA encoding the yeast phosphatase is dramatically induced by nitrogen starvation. Inactivation of the yeast phosphatase gene results in a decrease in growth rate.
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PMID:A yeast protein phosphatase related to the vaccinia virus VH1 phosphatase is induced by nitrogen starvation. 133 59

Proteose-peptone-activated mouse macrophages can prevent productive infection by herpes simplex virus in neighboring cells in vitro whether or not those cells belong to the same animal species. The effect does not require contact between the macrophages and the infected cells, may be prevented by adding extra arginine to the medium, and may be reversed when extra arginine is added 24 h after the macrophages. Arginase activity was found both intracellularly and released from the macrophages. The extracellular enzyme is quite stable; 64% activity was found after 48 h of incubation at 37 degrees C in tissue culture medium. No evidence was found that the inefficiency of virus replication in macrophages was due to self-starvation by arginase. As might be predicted macrophages can, by the same mechanism, limit productive infection by vaccinia virus.
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PMID:Inhibition of herpes simplex virus multiplication by activated macrophages: a role for arginase? 628 97

Phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2) is a well characterized mechanism regulating protein synthesis. Viral and cellular proteins have been identified that regulate the activity of the eIF-2alpha kinases. The regulatory protein, K3L, from vaccinia virus is homologous to the amino terminus of eIF-2alpha and is thought to inhibit the activity of the double-stranded RNA-dependent kinase suppressing the antiviral mechanism mediated by this kinase. We investigated whether K3L can inhibit the activity of the yeast eIF-2alpha kinase GCN2. Expression of K3L protein in yeast reduced the level of eIF-2alpha phosphorylation by GCN2 and blocked the stimulation of the general amino acid control pathway in response to starvation conditions. Accompanying in vitro studies showed that recombinant K3L protein reduced GCN2 autophosphorylation and phosphorylation eIF-2alpha. In agreement with the hypothesis that K3L inhibits eIF-2alpha kinases by functioning as a pseudosubstrate, we observed that K3L directly interacted with the kinase catalytic domain of GCN2. Together, these results indicate that K3L is a specific inhibitor of eIF-2alpha kinases from mammals and yeast and suggest that the kinases contain common structural features important for recognition of their substrate eIF-2alpha.
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PMID:Expression of vaccinia virus K3L protein in yeast inhibits eukaryotic initiation factor-2 kinase GCN2 and the general amino acid control pathway. 866 15

Regulation of vaccinia viral infection was studied using three animal cell lines: KRC-7 (rat hepatoma), L929 (mouse fibroblast), and CV-1 (African green monkey kidney). KRC-7 is highly enriched in p67, a glycoprotein which protects eIF-2 alpha-subunit from phosphorylation by eIF-2 kinases. We report: (i) At 5 pfu per cell of the virus, KRC-7 is resistant to the virus. Other cells are sensitive. At 25 pfu per cell of the virus, KRC-7 is also sensitive to the virus. After productive viral infection, the cell extracts showed strong p67-DG activity and actively deglycosylated exogenous p67. After p67-deglycosylation, the cell extracts also phosphorylated eIF-2. (ii) The rate of synthesis of a major host protein (approximately 45 kDa) in infected L929 cells measured after 2 h of viral infection declined more than 50%. The rate declined thereafter. The rate of synthesis of host proteins in viral-resistant KRC-7 cells (infected with 5 pfu per cell of the virus) remained unchanged. The mechanism of resistance of KRC7 cells to vacinia virus at 5 pfu per cell of the virus was investigated. The p67 level in these cells was varied by growing the cells under different physiological conditions such as serum starvation and expression of p67-sense and p67-antisense DNA. At low p67 level in the cells, p67-DG is activated. This deglycosylates p67 and inactivates p67. This accompanies eIF-2 phosphorylation and shutoff of host protein synthesis. At high p67 level in the cells, activation of p67-DG is prevented. This prevents shut-off of host protein synthesis and viral growth.
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PMID:Viral infection. I. Regulation of protein synthesis during vaccinia viral infection of animal cells. 918 99

Methionine aminopeptidases (MAPs) play important roles in protein processing. MAPs from various organisms, for example E. coli, S. typhimurium, P. furiosus, Saccharomyces cerevisiae, and porcine have been purified to homogeneity and their MAP activities have been tested in vitro and in vivo. The DNA sequence analyses of MAP genes from the above organisms reveal sequence homologies with other prokaryotic MAPs as well as with various eukaryotic homologues of rat p67. The cellular glycoprotein, p67 protects the alpha-subunit of eukaryotic initiation factor 2 (eIF2) from phosphorylation by its kinases. We call this POEP (protection of eIF2alpha phosphorylation) activity of p67. The POEP activity of p67 is observed in different stress-related situations such as during heme-deficiency of reticulocytes, serum starvation and heat-shock of mammalian cells, vaccinia virus infection of mammalian cells, baculovirus infection of insect cells, mitosis, apoptosis, and possibly during normal cell growth. The POEP activity of p67 is regulated by an enzyme, called p67-deglycosylase (p67-DG). When active, p67-DG inactivates p67 by removing its carbohydrate moieties. Remarkable amino acid sequence similarities at the C-terminus of rat p67 with its eukaryotic and prokaryotic homologues which have MAP activities, raise several important questions: i) does rat p67 have MAP activity?; and ii) if it does have MAP activity, how the two activities (POEP and MAP) of p67 are used by mammalian cells during their growth and differentiation. In this review, discussions have been made to evaluate both POEP and MAP activities of p67 and their possible involvement during normal growth and cancerous growth of mammalian cells.
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PMID:MAPs and POEP of the roads from prokaryotic to eukaryotic kingdoms. 1072 64

Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the rate-limiting enzyme in glucosamine synthesis. Prior studies from our laboratory indicated that activation of adenylate cyclase was associated with depletion of O-GlcNAc modification. This finding and evidence that human GFAT (hGFAT) might be regulated by cAMP-dependent protein kinase (PKA) led us to investigate the role of PKA in hGFAT function. We confirmed that adenylate cyclase activation by forskolin results in diminished O-GlcNAc modification of several cellular proteins which can be overcome by exposure of the cells to glucosamine but not glucose, suggesting the PKA activation results in depletion of UDP-GlcNAc for O-glycosylation. To determine if GFAT is indeed regulated by PKA, we expressed the active form of the enzyme using a vaccinia virus expression system and showed that the activity of the enzyme was to decrease to undetectable levels by PKA phosphorylation. We mapped the PKA phosphorylation sites with the aid of matrix-assisted laser desorption ionization mass spectroscopy and showed that the protein was stoichiometrically phosphorylated at serine 205 and also phosphorylated, to a lesser extent at serine 235. Mutagenesis studies indicated that the phosphorylation of serine 205 by PKA was necessary for the observed inhibition of enzyme activity while serine 235 phosphorylation played no observable role. The activity of GFAT is down-regulated by cAMP, thus placing regulation on the hexosamine pathway that is in concert with the energy requirements of the organism. During starvation, hormones acting through adenylate cyclase could direct the flux of glucose metabolism into energy production rather than into synthetic pathways that require hexosamines.
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PMID:Phosphorylation of human glutamine:fructose-6-phosphate amidotransferase by cAMP-dependent protein kinase at serine 205 blocks the enzyme activity. 1080 97

The Saccharomyces cerevisiae dual-specificity protein phosphatase Yvh1p, identified as vaccinia VH1 homolog, regulates cell growth, sporulation, and glycogen accumulation. Transcription of YVH1 is induced by lowering temperature and nitrogen starvation. Using the yeast two-hybrid system, we searched for Yvh1p-interacting proteins, including substrates and regulatory subunits of Yvh1p. Two clones were identified encoding a segment of YPH1 (yeast pescadillo homolog), which is essential for cell cycle progression in yeast. Deletion analysis revealed that the catalytic domain of Yvh1p and the BRCT domain of Yph1p are sufficient for this interaction. We found that the multicopy of YPH1 not only suppressed slow growth but also decreased IME2 expression in the yvh1 disruptant. These observations indicate that Yph1p plays a role in sporulation in addition to cell cycle progression, and is a candidate for a substrate or a regulatory subunit of Yvh1p.
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PMID:Dual-specificity protein phosphatase Yvh1p, which is required for vegetative growth and sporulation, interacts with yeast pescadillo homolog in Saccharomyces cerevisiae. 1171 19

Experiments are reported in which it is shown that if rabbits are deprived of food, the lesions resulting from injection of vaccinia are either fewer or smaller; presumably this is partially explainable on reduction of available nutrients in the cell. The number and character of the lesions are also modified by the state of hydration of the interstitial tissues: If the amount of interstitial fluid is increased by permitting the animal to drink water, the lesions are even less numerous; but if the interstitial tissues are dehydrated either by withholding water or by injecting physiological saline solution into the peritoneal cavity, then the lesions are more numerous. The increase in interstitial fluids in these experiments was not due to decreased plasma proteins, for these were normal. In this respect, therefore, the rabbit differs from man, for unless the plasma proteins are reduced, simple starvation in man results in dehydration rather than edema of the tissues. From these experiments it is concluded that the virus is less able to multiply in the poorly nourished cell than in the well nourished one, and that hydration of the tissues increases the resistance of the tissue to infection while dehydration has the opposite effect. It is suggested that this is because hydration tends to localize the virus in situ, with result that fewer cells are exposed to it, while dehydration has the opposite effect. However, actual changes in cell susceptibility consequent upon altered water balance may be responsible for the effect.
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PMID:THE EFFECT OF UNDERNOURISHMENT ON THE SUSCEPTIBILITY OF THE RABBIT TO INFECTION WITH VACCINIA. 1987 Nov 84