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

In mammals, glucose transport is mediated by five structurally related glucose transporters that show a characteristic cell-specific expression. However, the rat brain/HepG2/erythrocyte-type glucose transporter GLUT-1 is expressed at low levels in most cells. The reason for this coexpression is not clear. GLUT-1 is negatively regulated by glucose. Another family of proteins, glucose-regulated proteins (GRPs), is also ubiquitously expressed and stimulated by glucose deprivation and other cellular stresses. We therefore hypothesized that GLUT-1 may be a glucose-regulated stress protein. This was tested by subjecting L8 myocytes and NIH 3T3 fibroblasts to glucose starvation or exposure to the calcium ionophore A23187, 2-mercaptoethanol, or tunicamycin, all known to increase GRP levels. The mRNA for GLUT-1 was augmented by 50-300% in a time-dependent manner, similarly to the changes in GRP-78 mRNA. Ex vivo incubation of rat soleus muscles induced a marked and concomitant rise in the mRNA levels of GLUT-1 and GRP-78. Finally, calcium ionophore A23187 and 2-mercaptoethanol induced a 2- to 3-fold increase in the levels of the GLUT-1 protein and hexose uptake. In all instances in which GRP-78 and GLUT-1 responded to stress, the transcription of the cell-specific muscle/adipocyte-type insulin-responsive glucose transporter (GLUT-4) did not change. Thus, despite the lack of structural similarity, GLUT-1 and GRP-78 expression is regulated similarly, whereas the regulation of GLUT-4, which is structurally related to GLUT-1, is different. We propose that GLUT-1 belongs to the GRP family of stress proteins and that its ubiquitous expression may serve a specific purpose during cellular stress.
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PMID:The ubiquitous glucose transporter GLUT-1 belongs to the glucose-regulated protein family of stress-inducible proteins. 170 26

Induction of heat shock-related stress proteins Pfhsp and Pfgrp, similar in sequence to hsp70 (heat shock protein) and grp78 (glucose-regulated protein), respectively, was studied in culture-derived parasite Plasmodium falciparum. Elevation in temperature from 26 degrees C to 37 degrees C and higher caused significant induction of Pfhsp with a moderate effect on the synthesis of Pfgrp also. Synthesis of Pfgrp, however, was not induced by partial glucose deprivation. On the contrary, lack of glucose in the medium resulted in cessation of protein synthesis in the parasites. Other known inducers of grp synthesis in mammalian cells, i.e., calcium ionophore A23187 and inhibitors of glycosylation (tunicamycin, 2-deoxy glucose) were also without any apparent effect on the synthesis of Pfgrp. Heat shock-induced responses were transient in nature: removal of stress caused repression of these responses. The effect of glucose deprivation was only partially reversible with better recovery if parasites were subjected to glucose starvation at 26 degrees C than at 37 degrees C. Northern blot analysis and in vitro translation of mRNA revealed a parallel increase in the levels of mRNA for Pfhsp upon heat shock. Immuno-gold electron microscopy with cultured parasites revealed nuclear location of Pfhsp and primarily cytoplasmic (probably endoplasmic reticulum) location of Pfgrp. These findings suggest that SDEL (carboxy terminal sequence of Pfgrp) might play a similar role in the cellular localization of Pfgrp as does the sequence KDEL in mammalian cells and HDEL in yeast.
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PMID:Induction and localization of Plasmodium falciparum stress proteins related to the heat shock protein 70 family. 177 89

Starvation of a mouse hepatoma cell line, Hepa, for any essential amino acid results in the mono-ADP-ribosylation of an 80-kDa protein, P80. The ADP-ribose acceptor and its putative precursor were identified in two-dimensional gel patterns and isolated by electroelution. Amino-terminal sequence analysis showed they were the 78-kDa glucose-regulated protein, GRP78. Starvation of Hepa cells for tryptophan or glucose stimulated the relative rate of synthesis, and the ADP-ribosylation of GRP78. Inhibition of N-linked glycosylation by treatment with tunicamycin, 2-deoxy-D-glucose or glucosamine stimulated the synthesis of non-ADP-ribosylated GRP78 up to sixfold with relatively little effect on its ADP-ribosylation. Both forms were identified in mouse liver, lung, heart, kidney, spleen and brain.
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PMID:ADP-ribosylation of the 78-kDa glucose-regulated protein during nutritional stress. 251 84

Animal cells respond to calcium ionophore (A23187) treatment with the coordinate induction of a set of genes encoding proteins identical to the glucose-regulated proteins (GRPs). By monitoring the intracellular free calcium with the fluorescent indicator fura-2 while employing both intracellular and extracellular calcium buffers, we demonstrated that A23187 can induce the GRP94 and GRP78 genes without an increase in cytoplasmic calcium ([Ca2+]i). Induction of GRP mRNA during glucose starvation was also independent of [Ca2+]i. Instead, gene induction by A23187 was closely correlated with the depletion of intracellular calcium stores. We conclude that perturbations of sequestered calcium ions by A23187 can serve as a stimulus for gene expression.
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PMID:Depletion of intracellular calcium stores by calcium ionophore A23187 induces the genes for glucose-regulated proteins in hamster fibroblasts. 311 64

The 78,000-dalton glucose-regulated protein (GRP78) and the immunoglobulin heavy-chain-binding protein (BiP) were shown to be the same protein by NH2-terminal sequence comparison. Immunoprecipitation of GRP78-BiP induced by glucose starvation and a temperature-sensitive mutation in a hamster fibroblast cell line demonstrated the association of GRP78-BiP with other cellular proteins. In both fibroblasts and lymphoid cells, GRP78-BiP was found to label with 32Pi and [3H]adenosine. Phosphoamino acid analysis demonstrated that GRP78-BiP is phosphorylated on serine and threonine residues. Conditions which induce increased production of GRP78-BiP resulted in decreased incorporation of 32Pi and [3H]adenosine into GRP78-BiP. Furthermore, we report here that the phosphorylated form of BiP resides in the endoplasmic reticulum and that BiP which is associated with heavy chains is not phosphorylated or labeled with [3H]adenosine, whereas free BiP is. This suggests that posttranslational modifications may be important in regulating the synthesis and binding of BiP.
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PMID:Identity of the immunoglobulin heavy-chain-binding protein with the 78,000-dalton glucose-regulated protein and the role of posttranslational modifications in its binding function. 314 86

The 78-kDa glucose-regulated protein GRP78 is a stress-inducible protein ubiquitously expressed in animal cells. In this paper we show that the first exon of this endoplasmic reticulum-localized protein consists of an 18 amino acid leader sequence rich in hydrophobic residues, followed by a highly acidic mature N-terminus and an 11 amino acid domain that is shared by members of the 70-kDa heat shock protein family. The end of this shared domain also marks the beginning of the first intron of this gene. A DNA region upstream of the promoter element important for induction by calcium ionophore and by a temperature-sensitive mutation was identified by deletion analysis. Our results indicate that a region spanning from 85 to 480 nucleotides upstream of the major transcription initiation site is important for both induction conditions. With evidence suggesting that perturbations in protein glycosylation may be one of the common stimuli involved in transcription activation of the GRPs, we measured the rate of glycosylation during A23187, glucose starvation, and temperature-shift induced conditions. The inverse correlation observed between the rate of glycosylation and the steady-state level of the GRP78 transcripts lends support to this hypothesis.
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PMID:Rat gene encoding the 78-kDa glucose-regulated protein GRP78: its regulatory sequences and the effect of protein glycosylation on its expression. 346 6

The sulfhydryl-reducing agent beta-mercaptoethanol preferentially stimulates the synthesis of glucose-regulated proteins (GRPs) in mammalian cells. The rapid and large increase in GRPs is due to transcriptional activation of GRP94 and GRP78 genes, resulting in a rapid increase in the steady-state levels of GRP transcripts. From analysis of 5'-deletion mutants, the region of beta-mercaptoethanol responsiveness in the GRP78 promoter was mapped within 450 nucleotides upstream of the TATA sequence. This same general region was demonstrated to be important for induction of the GRP78 gene by the calcium ionophore A23187, glucose starvation, and a temperature-sensitive mutation in a K12 cell line defective in protein glycosylation.
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PMID:Transcriptional activation of the glucose-regulated protein genes and their heterologous fusion genes by beta-mercaptoethanol. 367 Mar 3

Confluent monolayer cultures of the bovine kidney cell line NBL-1 were starved of amino acids in the presence of tracer concentrations of [35S]-methionine. Fluorographs of SDS-polyacrylamide gel separated membrane proteins revealed increased labelling of at least two proteins in starved cells relative to those in cells grown in complete medium. The patterns of Coomassie blue stained proteins from Concanavalin A-purified fractions of cells grown under fed and amino acid-starved conditions were similar but fluorography indicated the presence of one major labelled glycoprotein with a molecular weight of 62 kD in starved cells which was not present in fed cells. N-terminal amino acid analysis of the first 15 amino acids of the 62 kD protein and a protein of 60 kD found in control cells identified both proteins as calreticulin. N-terminal amino acid sequence analysis of a second amino acid starvation-up-regulated protein identified it as glucose-regulated protein GRP78. The amino acid sequences of calreticulin, GRP78 and two transport proteins known to be induced in amino acid starvation, have a common motif near the C-terminal end of the molecule. It is suggested that calreticulin is a member of a novel class of stress proteins induced by amino acid starvation.
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PMID:Calreticulin--a stress protein induced in the renal epithelial cell line NBL-1 by amino acid deprivation. 795 7

The nucleotide sequence of the gene encoding the glucose-regulated protein 78 (GRP78) of Neurospora crassa was determined. The ORF codes for a protein of 662 amino acids (72 kDa) and belongs to the heat shock protein 70 (hsp70) gene family, which is characterized by three HSP70 'signature sequences'. The grp78 gene contains 5 introns. The protein carries the ER retention signal HDEL at its carboxy terminus and is most homologous to the KAR2/GRP78 protein of Saccharomyces cerevisiae (78%) and to KAR2/BiP of Yarrowia lipolytica (76%). The expression of grp78 is constitutive and can be enhanced by starvation, treatment with tunicamycin, the calcium ionophore A23187 or elevated temperatures (40 degrees C). An uninterrupted ORF was found on the reverse cDNA strand of grp78. The putative peptide shows 47% homology to the NAD-specific glutamate dehydrogenase of Achlya klebsiana.
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PMID:Molecular analysis of a glucose-regulated gene (grp78) of Neurospora crassa. 954 20

The endoplasmic reticulum chaperone glucose-regulated protein 78 (GRP78) is essential for the proper glycosylation, folding and assembly of many membrane bound and secreted proteins. GRP78 mRNA is well known to be induced in cultured cells by lowering medium glucose concentrations from 4.5 to 0 mg/ml. Here we report a study designed to determine the effects of intermediate concentrations of glucose on GRP78 mRNA abundance. Progressive reduction in culture medium glucose from 4.5 to 1.0 mg/ml progressively reduced GRP78 mRNA to approximately 30% of the initial level. Induction of GRP78 mRNA by glucose starvation was observed in medium containing less than 1 mg/ml glucose. Determination of the amount of glucose consumed in these cultures showed that reduction of glucose concentrations led first to repression of GRP78 mRNA abundance, followed by induction of the mRNA only when glucose is nearly exhausted. Caloric restriction in mice both reduces fasting and mean 24 h glucose blood concentrations and GRP78 mRNA abundance in the liver. Thus, it is possible that negative regulation of GRP78 mRNA in the liver is due directly to reduced blood glucose concentrations.
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PMID:Glucose regulation of GRP78 gene expression. 979 93


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