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)

In Neurospora crassa, heat shock results in the induction of 9 to 11 heat shock proteins (HSP), of which HSP80 is the most abundant and the first to be synthesized. The induction of HSP80 was investigated during normal growth (2% sucrose) and under sucrose starvation. Transfer of mycelium to a medium supplemented with ethanol stimulated the synthesis of HSP80, even at the normal growth temperature of 28 degrees C. It was also synthesized under carbon starvation conditions, where the medium was supplemented with 0.02% sucrose, 0.3% acetate, 0.2% lactate, or ethanol. A 30-35 kilodalton polypeptide was induced by heat shock in carbon-sufficient media, but in 0.02% sucrose and 0.3% acetate containing media it was synthesized at normal temperatures. While the overall heat shock response remained unaltered in these cultures, the abundance of HSP90 and HSP70, relative to HSP80, was greater. HSP80 appears to be controlled by carbon-catabolite repression as well as heat shock. Another high molecular mass protein (tentatively designated alc'80') was observed to be induced by heat shock, provided carbon starvation conditions prevailed concurrently.
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PMID:Ethanol and carbon-source starvation enhance the accumulation of HSP80 in Neurospora crassa. 296 70

Previously we have found that stationary Ehrlich ascites carcinoma (EAC) cells in vivo accumulated heat shock proteins (HSPs) and became resistant to necrotic death induced by prolonged energy deprivation of hyperthermia. Here we report that apoptotic death induced by nutrient starvation, transient ATP depletion, heat shock and a microtubule-disrupting drug, vinblastine, was also suppressed in stationary EAC cells comparing with exponential cells. When exponential (sensitive) cells were subjected to short-term heating with recovery to accumulate inducible form of HSP70, they also became resistant to all of the employed apoptosis-inducing exposures, and an inhibitor of cytosolic protein synthesis, cycloheximide, prevented acquisition of the resistance. It is suggested that in vivo accumulation of HSPs in stationary tumor cells can be endogenous protective device against apoptotic death induced by starvation or some anticancer treatments.
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PMID:Resistance of Ehrlich tumor cells to apoptosis can be due to accumulation of heat shock proteins. 749 72

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

We previously reported that PKN, a fatty acid-activated serine/threonine protein kinase, translocates from the cytosol to the nucleus by stresses such as heat shock, sodium arsenite, and serum starvation. To clarify the role of PKN under heat stress, we examined whether PKN regulates the expression of heat shock proteins. Co-expression of heat shock transcription factor 1 (HSF1) and the catalytically active fragment of PKN induced the accumulation of alphaB-crystallin but not HSP27 and HSP70 in HeLa S3 cells. The expression of the reporter gene for alphaB-crystallin promoter was activated by co-expression of HSF1 and the catalytically active fragment of PKN, and this activation was dependent on the protein kinase activity of PKN. Deletion analysis of the alphaB-crystallin promoter region revealed that both the proximal and the distal heat shock elements were necessary for the transactivation. These results raise the possibility that there is a signal transduction pathway mediating stress signals for the accumulation of alphaB-crystallin by HSF1 and PKN.
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PMID:The role of PKN in the regulation of alphaB-crystallin expression via heat shock transcription factor 1. 983 46

The heat shock response, which is characterized by the induction of heat shock proteins, is known to affect the ability of tumour cells to cope with potentially adverse conditions such as hypoxia, glucose starvation and cytotoxic immune reactions. To assess the heat shock response of melanoma cells, spontaneous and heat shock induced expression of heat shock proteins was analysed in a panel of 17 human melanoma cell lines. Constitutive expression of HSP27, HSP70, HSC70, HSP90alphabeta and GRP94 proteins was found in all the melanoma cell lines, and HSP70 and HSC70 were also induced by heat shock. The major heat inducible HLA-linked HSP70-1 and HSP70-2 genes were analysed at the mRNA level. Basal expression and inducibility varied between the different melanoma cell lines. In addition, in situ hybridization demonstrated heterogeneous expression of these genes among single cells of a given cell line. In general, each melanoma cell line appears to exhibit an individual type of HSP70 expression that might reflect selection during tumour progression and therapy.
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PMID:Heterogeneous patterns of constitutive and heat shock induced expression of HLA-linked HSP70-1 and HSP70-2 heat shock genes in human melanoma cell lines. 991 9

The yeast UME3 (SRB11/SSN3) gene encodes a C-type cyclin that represses the transcription of the HSP70 family member SSA1. To relieve this repression, Ume3p is rapidly destroyed in cells exposed to elevated temperatures. This report demonstrates that Ume3p levels are also reduced in cultures subjected to ethanol shock, oxidative stress, or carbon starvation or during growth on nonfermentable carbons. Of the three elements (RXXL, PEST, and cyclin box) previously shown to be required for heat-induced Ume3p destruction, only the cyclin box regulates Ume3p degradation in response to these stressors. The one exception observed was growth on nonfermentable carbons, which requires the PEST region. These findings indicate that yeast cells contain multiple, independent pathways that mediate stress-induced Ume3p degradation. Ume3p destruction in response to oxidative stress, but not to ethanol treatment, requires DOA4 and UMP1, two factors required for 26S proteasome activity. This result for the first time implicates ubiquitin-mediated proteolysis in C-type cyclin regulation. Similarly, the presence of a membrane stabilizer (sorbitol) or the loss of phosphatidylinositol-specific phospholipase C (PLC1) protects Ume3p from oxidative-stress-induced degradation. Finally, a ume3 null allele suppresses the growth defect of plc1 mutants in response to either elevated temperature or the presence of hydrogen peroxide. These results indicate that the growth defects observed in plc1 mutants are due to the failure to downregulate Ume3p. Taken together, these findings support a model in which Plc1p mediates an oxidative-stress signal from the plasma membrane that triggers Ume3p destruction through a Doa4p-dependent mechanism.
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PMID:Oxidative stress-induced destruction of the yeast C-type cyclin Ume3p requires phosphatidylinositol-specific phospholipase C and the 26S proteasome. 1020 58

Our previous work in neuronal cultures has shown that several antagonists of P2 ATP receptors prevent cell death evoked by hypoglycaemia, chemical hypoxia, mitochondria dysfunction, as well as glutamate-dependent excitotoxicity and low potassium-induced apoptosis. Experiments are now designed to examine which biological pathway contributes to cell death/survival under glucose starvation. We show here that, consequently to hypoglycaemic insults, cerebellar granule neurones undergo a combination of apoptosis and necrosis both inhibited by the P2 receptor antagonist basilen blue. This is demonstrated by morphological and biochemical features, such as TdT-mediated dUTP-biotin nick end-labelling, fluorescent staining of nuclear chromatin using Hoechst 33258, direct counting of intact viable nuclei and extracellular releasing of the cytosolic enzyme LDH. Furthermore, we show that hypoglycaemia induces outflow of cytochrome c from mitochondria and it up-regulates heat-shock proteins HSP70, but not HSP90, glucose-regulated proteins GRP75 and GRP78, as well as expression and activity of the enzyme caspase-2. Basilen blue can modulate only some of these effects. Our data contribute to dissect the role played by P2 receptor antagonism in sustaining neuroprotection against metabolic stresses.
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PMID:Hypoglycaemia-induced cell death: features of neuroprotection by the P2 receptor antagonist basilen blue. 1109 77

We previously demonstrated the protective effect of inducible heat shock protein 70 (Hsp70) against gamma radiation. Herein, we extend our studies on the possible role of Hsp70 to ionizing radiation-induced cell cycle regulation. The growth rate of inducible hsp70-transfected cells was 2-3 hours slower than that of control cells. Flow cytometric analysis of cells at G1 phase synchronized by serum starvation also showed the growth delay in the Hsp70-overexpressing cells. In addition, reduced cyclin D1 and Cdc2 levels and increased dephosphorylated phosphoretinoblastoma (pRb) were observed in inducible hsp70-transfected cells, which were probably responsible for the reduction of cell growth. To find out if inducible Hsp70-mediated growth delay affected radiation-induced cell cycle regulation, flow cytometric and molecular analyses of cell cycle regulatory proteins and their kinase were performed. The radiation-induced G2/M arrest was found to be inhibited by Hsp70 overexpression and reduced p21Waf induction and its kinase activity by radiation in the Hsp70-transfected cells. In addition, radiation-induced cyclin A or B1 expressions together with their kinase activities were also inhibited by inducible Hsp70, which represented reduced mitotic cell death. Indeed, hsp70 transfectants showed less induction of radiation-induced apoptosis. When treated with nocodazole, radiation-induced mitotic arrest was inhibited by inducible Hsp70. These results strongly suggested that inducible Hsp70 modified growth delay (increased G1 phase) and reduced G2/M phase arrest, subsequently resulting in inhibition of radiation-induced cell death.
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PMID:Role of inducible heat shock protein 70 in radiation-induced cell death. 1159 69

The human oesophageal epithelium is subject to damage from thermal stresses and low extracellular pH that can play a role in the cancer progression sequence, thus identifying a physiological model system that can be used to determine how stress responses control carcinogenesis. The classic heat shock protein HSP70 is not induced but rather is down-regulated after thermal injury to squamous epithelium ex vivo; this prompted a longer-term study to address the nature of the heat shock response in this cell type. An ex vivo epithelial culture system was subsequently used to identify three major proteins of 78, 70, and 58 kDa, whose steady-state levels are elevated after heat shock. Two of the three heat shock proteins were identified by mass spectrometric sequencing to be the calcium-calmodulin homologue transglutaminase-3 (78 kDa) and a recently cloned oesophageal-specific gene called C1orf10, which encodes a 53-kDa putative calcium binding protein we have named squamous epithelial heat shock protein 53 (SEP53). The 70-kDa heat shock protein (we have named SEP70) was not identifiable by mass spectrometry, but it was purified and studied immunochemically to demonstrate that it is distinct from HSP70 protein. Monoclonal antibodies to SEP70 protein were developed to indicate that: (a) SEP70 is induced by exposure of cultured cells to low pH or glucose starvation, under conditions where HSP70 protein was strikingly down-regulated; and (b) SEP70 protein exhibits variable expression in preneoplastic Barrett's epithelium under conditions where HSP70 protein is not expressed. These results indicate that human oesophageal squamous epithelium exhibits an atypical heat shock protein response, presumably due to the evolutionary adaptation of cells within this organ to survive in an unusual microenvironment exposed to chemical, thermal and acid reflux stresses.
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PMID:The human oesophageal squamous epithelium exhibits a novel type of heat shock protein response. 1160 97

During sepsis and major trauma the blood glutamine (Gln) level is reduced. The administration of Gln can improve the outcome of these patients. However, the mechanism of this beneficial effect of Gln is poorly understood. In the course of critical illness leucocytes are confronted with cytotoxic inflammatory mediators. To protect themselves against these factors, cells express heat shock proteins (HSP). Previous studies have shown that the expression of the major inducible HSP (HSP70) is improved by high Gln concentrations above 4 mM. In this study we investigated whether Gln depletion, such as observed during critical illness, has an effect on HSP70 expression. Human lymphocytes exposed for 2 h to 42 degrees C showed a 3-fold increase in HSP70 expression (P<0.01). A preceding Gln starvation period over 3 days had no influence on this increase. However, when Gln is reduced during the stress response, HSP70 expression is impaired. A reduction of Gln from 0.5 mM (physiological) to 0.125 mM (pathological) led to a 40% lower HSP70 level (P<0.002). In contrast, increasing Gln concentrations (up to 2 mM) had only minor stimulatory effects (about 15%). This Gln-dependency of heat mediated HSP70 expression was observed in resting as well as proliferating lymphocytes. Our data indicate that during periods of reduced plasma Gln levels the stress response of human lymphocytes is impaired. Thus, Gln may be essential to minimize the susceptibility of leucocytes to cytotoxic inflammatory mediators. This is a new aspect of the protective effect of Gln supplementation in critically ill patients.
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PMID:Glutamine depletion impairs cellular stress response in human leucocytes. 1189 51


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