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)

The chemokine receptor CXCR4 functions as human immunodeficiency virus (HIV)-1 coreceptor and is involved in acquired immunodeficiency virus (AIDS) neuropathogenesis. CXCR4 is expressed by most cell types in the brain, including microglia, astrocytes, and neurons. Studies have shown that the HIV envelope protein gp120 binds to neuronal CXCR4 and activates signal transduction pathways leading to apoptosis. However, the natural CXCR4 ligand (CXCL12) has been referred to induce both neuronal survival and death. Here the authors used flow cytometry to determine whether gp120 and CXCL12 differ in their ability to induce CXCR4 internalization in the human neuroblastoma cells SH-SY5Y, which constitutively express CXCR4. As expected, increasing concentration of CXCL12 reduced surface expression of CXCR4 in a time-and concentration-dependent manner. Conversely, gp120IIIB (monomeric or oligomeric, in presence or absence of soluble CD4) did not change CXCR4 membrane levels. Similar results were obtained in a murine lymphocyte cell line (300-19) stably expressing human CXCR4. Nevertheless, gp120IIIB was still able to activate intracellular signaling and proapoptotic pathways, via CXCR4. These results show that gp120IIIB toxicity and signaling do not require CXCR4 internalization in SH-SY5Y cells, and suggest that the viral protein may alter normal CXCR4 trafficking thus, interfering with activation of prosurvival pathways.
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PMID:Human immunodeficiency virus gp120-induced apoptosis of human neuroblastoma cells in the absence of CXCR4 internalization. 1687 2

Chemokine receptors, and in particular CXCR4 and CCR5 play a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV)4 associated dementia (HAD). Thus, new insight into the expression of CXCR4 in the central nervous system may help develop therapeutic compounds against HAD. Brain-derived neurotrophic factor (BDNF) is neuroprotective in vitro against two strains of the HIV envelope protein gp120 that binds to CXCR4 or CCR5. Therefore, we examined whether BDNF modulates chemokine receptor expression in vivo. The content of CXCR4 mRNA and proteins was determined in the cerebral cortex and hippocampus of 6-month-old BDNF heterozygous mice and wild type littermates by using polymerase chain reaction and immunohistochemistry, respectively. BDNF heterozygous mice exhibited an increase in CXCR4 mRNA compared to wild type. Histological analyses revealed an up-regulation of CXCR4 immunoreactivity mainly in neurons. Most of these neurons were positive for TrkB, the BDNF receptor with a tyrosine kinase activity. Increases in CXCR4 mRNA levels were observed in 18-month-old BDNF heterozygous mice but not in 7-day-old mice, suggesting that the modulatory role of BDNF occurs only in mature animals. To determine whether BDNF affects also CXCR4 internalization, SH-SY5Y neuroblastoma cells were exposed to BDNF and cell surface CXCR4 levels were measured at various times. BDNF induced CXCR4 internalization within minutes. Lastly, BDNF heterozygous mice showed higher levels of CCR5 and CXCR3 mRNA than wild type in the cerebral cortex, hippocampus and striatum. Our data indicate that BDNF may modulate the availability of chemokine receptors implicated in HIV infection.
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PMID:Brain-derived neurotrophic factor modulates expression of chemokine receptors in the brain. 1858 60

Japanese encephalitis virus (JEV) envelope (E) protein has been shown to play a critical role in attachment to cells. However, the receptor interacting with envelope protein has not been conclusively identified. Using mouse neuroblastoma (Neuro2a) cells and purified JEV-E protein in 'Virus Overlay Protein Binding Assay' followed by MALDI-TOF analysis, we identified 'heat shock protein 70' (Hsp70) as a possible receptor for JEV. Indirect immunofluorescence and flow-cytometry analysis demonstrated localization of Hsp70 on Neuro2a cell surface. Co-immunoprecipitation followed by Western blot analysis reconfirmed the interaction between Hsp70 and JEV-E protein. Further, anti-Hsp70 polyclonal-antibodies were able to block JEV entry into Neuro2a cells. Additionally, using the bioinformatic tool - FTDOCK, docking between the proteins was performed. Amongst six interacting structural poses studied one pose involving RGD motif on JEV-E and leucine(539) on Hsp70 displayed stable interaction. These observations indicate that Hsp70 serves as putative receptor for JEV in Neuro2A cells.
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PMID:Heat shock protein 70 on Neuro2a cells is a putative receptor for Japanese encephalitis virus. 1906 61

Genetic stability is an important characteristic of live viral vaccines because an accumulation of mutants can cause reversion to a virulent phenotype as well as a loss of immunogenic properties. This study was aimed at evaluating the genetic stability of a live attenuated West Nile (WN) virus vaccine candidate that was generated by replacing the pre-membrane and envelope protein genes of dengue 4 virus with those from WN. Chimeric virus was serially propagated in Vero, SH-SY5Y human neuroblastoma and HeLa cells and screened for point mutations using hybridization with microarrays of overlapping oligonucleotide probes covering the entire genome. The analysis revealed several spontaneous mutations that led to amino acid changes, most of which were located in the envelope (E) and non-structural NS4A, NS4B, and NS5 proteins. Viruses passaged in Vero and SH-SY5Y cells shared two common mutations: G(2337) C (Met(457) Ile) in the E gene and A(6751) G (Lys(125) Arg) in the NS4A gene. Quantitative assessment of the contents of these mutants in viral stocks indicated that they accumulated independently with different kinetics during propagation in cell cultures. Mutant viruses grew better in Vero cells compared to the parental virus, suggesting that they have a higher fitness. When tested in newborn mice, the cell culture-passaged viruses did not exhibit increased neurovirulence. The approach described in this article could be useful for monitoring the molecular consistency and quality control of vaccine strains.
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PMID:Microarray hybridization for assessment of the genetic stability of chimeric West Nile/dengue 4 virus. 2136 May 44


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