UMLS:C0027819 - FACTA Search

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In neuroblastoma cells, apoptotic programs can be activated by cytokines and cytostatic drugs. Apoptotic dysfunction confers resistance against therapeutic drugs and is a major complication for achieving optimal therapy response. Deregulated expression of the MYCN gene is a critical determinant in neuroblastoma progression, and one of the pleiotropic functions of the MYCN protein is cellular sensitization to cytokine-induced and drug-induced apoptosis. By using the functional approach of technical knockout (TKO), we have identified five genes that regulate sensitization for IFN-gamma-induced cell death. Most efficient among them is the newly identified SOXN (neuroblastoma-derived sulfhydryl oxidase), which comprises 12 exons and maps to 9q34.3. SOXN encodes a putative protein of 698 amino acids that contains a signal sequence, a protein-disulfide-isomerase-type thioredoxin and a yeast ERV1 domain and is highly homologous to members of the sulfhydryl oxidase/Quiescin6 family. The SOXN protein is predominantly located in the plasma and in the nuclear membrane. Antisense SOXN confers resistance to IFN-gamma-induced apoptosis. In contrast, ectopic overexpression of sense-SOXN sensitizes the cells to induced cell death. These results identify SOXN as a major player in regulating the sensitization of neuroblastoma cells for IFN-gamma-induced apoptosis.
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PMID:Neuroblastoma-derived sulfhydryl oxidase, a new member of the sulfhydryl oxidase/Quiescin6 family, regulates sensitization to interferon gamma-induced cell death in human neuroblastoma cells. 1463 99

The mammalian growth factor erv1-like (GFER) gene encodes a sulfhydryl oxidase enzyme, named Augmenter of Liver Regeneration (ALR). Recently it has been demonstrated that ALR supports cell proliferation acting as an anti-apoptotic factor. This effect is determined by ALR ability to support the anti-apoptotic gene expression and to preserve cellular normoxic conditions. We recently demonstrated that the addition of recombinant ALR (rALR) in the culture medium of H(2)O(2)-treated neuroblastoma cells reduces the lethal effects induced by the hydrogen peroxide. Similar data have been reported in the regenerating liver tissue from partially hepatectomized rats treated with rALR. The purpose of the present study was to evaluate the effect of the GFER inhibition, via the degradation of the complementary mRNA by the specific siRNA, on the behaviour of the apoptosis (apoptotic gene and caspase expression and apoptotic cell number) and of the oxidative stress-induced parameters (reactive oxygen species (ROS), clusterin expression and mitochondrial integrity) in T98G glioma cells. The results revealed a reduction of (i) ALR, (ii) clusterin and (iii) bcl-2 and an increase of (iv) caspase-9, activated caspase-3, ROS, apoptotic cell number and mitochondrial degeneration. These data confirm the anti-apoptotic role of ALR and its anti-oxidative properties, and shed some light on the molecular pathways through which ALR modulates its biological effects.
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PMID:Decreased expression of the augmenter of liver regeneration results in increased apoptosis and oxidative damage in human-derived glioma cells. 2247 97

Prions are infectious proteins that cause a group of fatal transmissible diseases in animals and humans. The scrapie isoform (PrP^Sc) of the cellular prion protein (PrP^C) is the only known component of the prion. Several lines of evidence have suggested that the formation and molecular features of PrP^Sc are associated with an abnormal unfolding/refolding process. Quiescin-sulfhydryl oxidase (QSOX) plays a role in protein folding by introducing disulfides into unfolded reduced proteins. Here we report that QSOX inhibits human prion propagation in protein misfolding cyclic amplification reactions and murine prion propagation in scrapie-infected neuroblastoma cells. Moreover, QSOX preferentially binds PrP^Sc from prion-infected human or animal brains, but not PrP^C from uninfected brains. Surface plasmon resonance of the recombinant mouse PrP (moPrP) demonstrates that the affinity of QSOX for monomer is significantly lower than that for octamer (312 nM vs 1.7 nM). QSOX exhibits much lower affinity for N-terminally truncated moPrP (PrP89-230) than for the full-length moPrP (PrP23-231) (312 nM vs 2 nM), suggesting that the N-terminal region of PrP is critical for the interaction of PrP with QSOX. Our study indicates that QSOX may play a role in prion formation, which may open new therapeutic avenues for treating prion diseases.
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PMID:Quiescin-sulfhydryl oxidase inhibits prion formation in vitro. 2795 66