Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heat shock-induced alterations in protein synthesis and the cytoskeleton of two mammalian cell types have been investigated. A hyperthermic treatment of 30 min at 43 degrees C causes an accumulation of heat shock proteins (HSPs). The apparent molecular weights of HSPs of Reuber H35 hepatoma cells and of N2A neuroblastoma cells are 28 000, 65 000, 68 000, 70 000, 84 000, 100 000 D and 68 000, 70 000, 84 000 and 100 000 D respectively. Hyperthermia induces the disruption of microfilaments in hepatoma cells. Microtubules and intermediate filaments (vimentin and cytokeratin) remain intact. In neuroblastoma cells microfilaments remain intact whereas microtubules become disorganized after heat shock. As a result vimentin is found as a perinuclear aggregate. These cells were still able to synthesize heat shock proteins after pretreatment with cytoskeleton disrupting drugs such as dihydroxycytochalasin B and colchicine. Therefore it is concluded that the alterations in the cytoskeleton observed after the heat treatment are unlikely to be the cause of heat shock protein synthesis. Our results suggest that these heat shock-induced alterations in the cytoskeleton can be considered as a part of the heat shock response.
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PMID:Studies on a possible relationship between alterations in the cytoskeleton and induction of heat shock protein synthesis in mammalian cells. 242 73

Electrophoretic analysis of cell proteins of 3 mouse neuroblastoma strains differing in thermostability has shown that a distinctive feature of one of the strains (stable to the action of temperature at 44 degrees C) is the accumulation under normal conditions (37 degrees C) of heat shock protein with the molecular mass of 70 kD. Such accumulation of the specific protein does not take place in cells of the thermosensitive strain, stable to temperature of 40 degrees C.
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PMID:[Expression of heat-shock proteins in neuroblastoma cells differing genetically in thermal sensitivity]. 360 Feb 26

A conditioning treatment of 30 min at 42 degrees C or 43 degrees C, followed by a 4-h recovery period at 37 degrees C, induces thermotolerance state in the cytoskeleton of Reuber H35 hepatoma cells and N2A neuroblastoma cells. Evidence for the involvement of heat shock proteins in the development of thermotolerance in the cytoskeleton has been obtained from the following observations: only those conditioning treatments inducing the enhanced synthesis of heat shock proteins (HSPs) are able to induce the heat-resistant state of the cytoskeleton; prevention of HSP synthesis by actinomycin D or cycloheximide also prevents the acquisition of thermotolerance in the cytoskeleton; an alternative inducer of HSP synthesis, sodium arsenite, is also able to induce the cytoskeletal thermotolerance; the kinetics of development and disappearance of thermotolerance in the cytoskeleton is parallel to the kinetics of accumulation and decay of HSPs. The possible function of HSPs in the heat-resistant cytoskeleton of H35 hepatoma and N2A neuroblastoma cells is discussed.
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PMID:Stress-induced thermotolerance of the cytoskeleton of mouse neuroblastoma N2A cells and rat Reuber H35 hepatoma cells. 381 63

Previously we found that ethanol increases expression of the constitutive 70-kDa heat shock protein (Hsc70) in NG108-15 neuroblastoma x glioma cells. We suggested that known ethanol actions on cellular protein trafficking may relate to Hsc70 induction because Hsc70 functions as a molecular chaperone. Here we use a subtractive hybridization protocol to isolate ethanol-responsive genes (EtRGs). Northern blot hybridization verified ethanol-induced increases in mRNA abundance for five cDNA clones isolated from ethanol-treated NG108-15 neuroblastoma x glioma cells. DNA sequence analysis identified one EtRG as 94-kDa glucose-regulated protein (GRP94), a member of the "glucose-responsive" subgroup of stress proteins. Other identified EtRGs included an insulin-induced growth-response protein gene and an intracisternal A-type particle gene. Sequence analysis of the remaining two EtRGs showed no homology in DNA sequence databases. All EtRGs showed wide tissue expression, except SL64, which was not detected in Northern blot analyses of adult mouse or rat tissues. Ethanol also increased mRNA abundance for 78-kDa glucose-regulated protein (GRP78), a molecular chaperone known to function in glycoprotein trafficking and usually coordinately regulated with GRP94. However, ethanol induced GRP94 more than GRP78, a pattern distinct from those of other inducers of these genes. All EtRGs, including GRP94 and GRP78, showed similar ethanol concentration-dependent increases in mRNA abundance. In contrast, thapsigargin and other inducers of glucose-responsive proteins increased GRP94 and GRP78 mRNA levels without altering expression of other EtRGs. Our studies demonstrate that several molecular chaperones constitute a subset of EtRGs. Ethanol appears to regulate these EtRGs by a unique mechanism, rather than one shared by classical inducers of stress proteins.
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PMID:Ethanol-responsive genes in neural cells include the 78-kilodalton glucose-regulated protein (GRP78) and 94-kilodalton glucose-regulated protein (GRP94) molecular chaperones. 796 74

The characteristic features of Alzheimer's disease (AD) include a high density of beta-amyloid-containing plaques in the cerebral cortex and the loss of basal forebrain cholinergic neurons. Amyloid beta-protein (A beta, Mr. approximately 4.5 kDa) is derived from a family of large (Mr. approximately 110-140 kDa) beta-amyloid precursor proteins (APP) which are integral membrane glycoproteins consisting of a large extracytoplasmic domain, a transmembrane domain, and a short cytoplasmic tail. Secreted derivatives of APP lacking the cytoplasmic tail, transmembrane domain, and a small portion of the extracellular domain are generated by the proteolytic processing of full length APP by a family of proteolytic enzymes known as APP secretases. Using cell cultures, we investigated the possibility that APP processing can be regulated by a centrally active cholinesterase inhibitor, tacrine, which has recently been shown to improve memory and cognitive functions in patients with AD. We analyzed the level of APP in glial, fibroblast, pheochromocytoma (PC12), and neuroblastoma cells by immunoblotting cell lysates and conditioned media. Normal levels of secretion of soluble APP derivatives by cells into conditioned media were severely inhibited by treating cells with tacrine. A similar decrease after treatment with tacrine was observed when neuroblastoma and PC12 cells were pretreated with either growth factors, phorbol ester, or retinoic acid. To determine whether the effect of tacrine on APP levels was specific or a more general phenomenon affecting other proteins, we measured the level of heat shock protein-70 (HSP-70) and another secretory protein, protease nexin-1 (PN-1). Tacrine treatment did not alter the level of HSP-70 in cell extracts and tacrine affected mildly the secretion of PN-1. Thus, the processing of HSP and PN-1, unlike APP, was not severely affected by treating cells with tacrine. Our results suggest that tacrine may inhibit an acetylcholinesterase-associated proteolytic activity involved in the secretion of APP, which results in less secretion of soluble APP into the conditioned media from tacrine treated cells. These results demonstrate that tacrine regulates APP secretion in cell cultures and suggest the possibility that tacrine therapy of Alzheimer's disease may, in the longer term, have effects on the process of A beta deposition.
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PMID:Tacrine alters the secretion of the beta-amyloid precursor protein in cell lines. 804 78

Heat-induced expression of 72-kDa heat shock protein (HSP72) was investigated in a panel of neuronal and non-neuronal cell lines by immunoblotting and immunocytochemistry using monoclonal antibodies directed to HSP72. By immunoblotting, HSP72 expression was observed in most cell lines of mouse (SN6.1b, CL8c4.7, NSC34.6, B2A, C2C12), rat (PC12, C-6, L3), and human (NB-1, GOTO, IMR-32, HeLa) origin under the heat-stressed condition. The mouse neuroblastoma cell line N18TG2, however, did not express HSP72 under the heat-stressed condition. By immunocytochemistry, HSP72 was undetectable in the heat-stressed N18TG2 cells, while it was identified in the heat-stressed SN6.1b cells, a clonal hybrid neuron between N18TG2 and mouse septal cholinergic neuron. By exposure to a priming sublethal heat shock, SN6.1b cells but not N18TG2 cells acquired a significant level of tolerance to a subsequent lethal heat shock. These results suggest that heat-induced expression of HSP72 may contribute to acquisition of the thermotolerant state in SN6.1b cells.
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PMID:HSP72 induction by heat stress is not universal in mammalian neural cell lines. 814 2

Previous in vitro work demonstrated the incorporation of the major inducible 70k heat shock protein (i.e., 72k HSP) into the biologically active light nucleocapsid (L-NC) variant of canine distemper virus (CDV). Here, in vitro induction of the cellular stress response, characterized by elevated cytoplasmic and intranuclear 72k HSP, enhanced L-NC expression in mink lung cells supporting stable persistent infection by raccoon-origin CDV. Increases in L-NC were correlated to increased viral RNA production in cell-free transcriptional assays. The enhanced production of viral transcripts within infected cells following stress response induction was confirmed by slot blot and Northern blot analysis of total cellular RNA and was reflected in increased total viral protein production. Post-shock increases in viral fusion (F) gene transcripts and F protein were associated with dramatic increases in viral cytopathic effect. Modest induction of cell-free infectious viral progeny was also documented. A similar effect of the cellular stress response upon viral protein expression, cytopathic effect, and cell-free infectious progeny release was demonstrated in murine neuroblastoma cells persistently infected with a canine CDV isolate. Alterations of the persistent viral phenotype were independent of the specific mechanism of stress-response induction (i.e., heat or sodium arsenite), supporting the role of the stress response and not a particular stressor in mediating these changes. These results document the ability of the cellular environment to alter persistent viral RNA metabolism, thereby altering the infection phenotype.
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PMID:Enhanced production of morbillivirus gene-specific RNAs following induction of the cellular stress response in stable persistent infection. 842

We studied heat shock protein (HSP) synthesis by cultured human neuroblastoma cells in response to either hyperthermia or high levels of superoxide anion (oxygen free radical). Both treatment modalities resulted in induced synthesis of the same major HSP species with an additive effect on the latter and on cell growth inhibition upon combined treatments. Exposure to superoxide anion in the presence of the free radical scavenging enzymes, superoxide dismutase and catalase improved cell survival and prevented HSP induction. These findings suggest a common mechanism by which various forms of injury, such as hyperthermia, cause HSP induction, that is, via oxidative stress or increased production of oxygen free radicals. Increased expression of some HSPs has been detected in association with the pathological lesions that characterize some neurodegenerative diseases such as the neurofibrillary tangles of Alzheimer's disease. This, in turn, suggests that chronic oxidative stress may play a role in the pathogenesis of these disorders.
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PMID:Oxygen free radicals as inducers of heat shock protein synthesis in cultured human neuroblastoma cells: relevance to neurodegenerative disease. 849 94

The neurotrophic property of the immunosuppressant drug FK506 (tacrolimus) is believed to depend on the 12-kDa FK506-binding protein (FKBP-12). Here, we show that FK506 maintains its neurotrophic activity in primary hippocampal cell cultures from FKBP-12 knockout mice. In human neuroblastoma SH-SY5Y cells, the neurotrophic action of FK506 (10 pM to 10 nM) is completely prevented by the addition of a monoclonal antibody (50-100 nM) to the immunophilin FKBP-52 (also known as FKBP-59 or heat shock protein 56), a component of mature steroid receptor complexes. By itself, the FKBP-52 antibody is also neurotrophic. The neurotrophic activity of dexamethasone (50 nM) is potentiated by FK506, whereas that of beta-estradiol (50 nM) is not altered, suggesting a common mechanisms of action. Geldanamycin (which disrupts mature steroid receptor complexes) is also neurotrophic (0.1-10 nM), whereas it reduces the neurotrophic activity of FK506 and steroid hormones (dexamethasone and beta-estradiol). Conversely, 20 mM molybdate (which prevents the disruption of mature steroid receptor complexes) decreases the neurotrophic activity of FK506, FKBP-52 antibody, dexamethasone, and beta-estradiol. In rats, FK506 (10 mg/kg s.c.) augments the regenerative response of regenerating motor and sensory neurons to nerve injury as shown by its ability to increase the axotomy-induced induction of c-jun expression. A model is proposed to account for the neurotrophic action of both neuroimmunophilin ligands (FK506) and steroid hormones. Components of steroid receptor complexes represent novel targets for the rational design of new neurotrophic drugs.
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PMID:Immunophilin FK506-binding protein 52 (not FK506-binding protein 12) mediates the neurotrophic action of FK506. 1033 7

Elevated temperatures activate the survival promoters Akt and heat shock factor-1 (HSF-1), a transcription factor that induces the expression of heat shock proteins (HSPs), such as HSP-70. Because neuronal mechanisms controlling these responses are not known, these were investigated in human neuroblastoma SH-SY5Y cells. Heat shock (45 degrees C) rapidly activated Akt, extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38, but only Akt was activated in a phosphatidylinositol 3-kinase (PI-3K)-dependent manner, as the PI-3K inhibitors LY294002 and wortmannin blocked Akt activation, but not ERK1/2 or p38 activation. Akt activation was not blocked by inhibition of p38 or ERK1/2, indicating the independence of these signaling systems. Heat shock treatment also caused a rapid increase in HSF-1 DNA binding activity that was partially dependent on PI-3K activity, as both the PI-3K inhibitors attenuated this response. Because Akt inhibits glycogen synthase kinase-3beta (GSK-3beta), an enzyme that facilitates cell death, we tested if GSK-3beta is a negative regulator of HSF-1 activation. Overexpression of GSK-3beta impaired heat shock-induced activation of HSF-1, and also reduced HSP-70 production, which was partially restored by the GSK-3beta inhibitor lithium. Thus, heat shock-induced activation of PI-3K and the inhibitory effect of GSK-3beta on HSF-1 activation and HSP-70 expression imply that Akt-induced inhibition of GSK-3beta contributes to the activation of HSF-1.
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PMID:Opposing actions of phosphatidylinositol 3-kinase and glycogen synthase kinase-3beta in the regulation of HSF-1 activity. 1108 Jan 91


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