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)

Reln mRNA and protein levels are reduced by approximately 50% in various cortical structures of post-mortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene. We show that the reelin promoter directs expression of a reporter construct in multiple human cell types: neuroblastoma cells (SHSY5Y), neuronal precursor cells (NT2), differentiated neurons (hNT) and hepatoma cells (HepG2). Deletion constructs confirmed the presence of multiple elements regulating Reln expression, although the promoter activity is promiscuous, i.e. activity did not correlate with expression of the endogenous gene as reflected in terms of reelin mRNA levels. Co-transfection of the -514 bp human reelin promoter with either Sp1 or Tbr1 demonstrated that these transcription factors activate reporter expression by 6- and 8.5-fold, respectively. Within 400 bp of the RNA start site there are 100 potential CpG targets for DNA methylation. Retinoic acid (RA)-induced differentiation of NT2 cells to hNT neurons was accompanied by increased reelin expression and by the appearance of three DNase I hypersensitive sites 5' to the RNA start site. RA-induced differentiation was also associated with demethylation of the reelin promoter. To test if methylation silenced reelin expression, we methylated the promoter in vitro prior to transfection. In addition, we treated NT2 cells with the methylation inhibitor aza-2'-deoxycytidine and observed a 60-fold increase in reelin mRNA levels. The histone deacetylase inhibitors trichostatin A (TSA) and valproic acid also induced expression of the endogenous reelin promoter, although TSA was considerably more potent. These findings indicate that one determinant responsible for regulating reelin expression is the methylation status of the promoter. Our data also raise the interesting possibility that the down-regulation of reelin expression documented in psychiatric patients might be the consequence of inappropriate promoter hypermethylation.
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PMID:On the epigenetic regulation of the human reelin promoter. 1208 79

Cell protrusive motility underlies cell fundamental biological processes such as cell growth, locomotion, and migration. Here I showed that selenium-binding protein (SBP) was exclusively located at the leading edges of rapidly growing protrusions in newly plated T98G glioma cells, and at the growing tips of the neurites in SH-SY5Y neuroblastoma cells. Double staining by anti-SBP antibody and deoxyribonuclease (DNase I) that labels monomeric G-actin or phalloidin that labels filamentous F-actin showed that the SBP-positive area was overstained by DNase I but, surprisingly, was not stained by phalloidin. When the cells were incubated with chemicals which block actin polymerization or activity of phosphatidylinositol 3-kinase, recruitment of SBP and G-actin at the cell margin was still observed, showing that their recruitment precedes actin polymerization. Taken together, I suggest that SBP may be involved in the initial sequential events in rapid cell outgrowth, such as determining direction of cell outgrowth and recruitment of actin monomer.
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PMID:Localization of selenium-binding protein at the tips of rapidly extending protrusions. 1510 3

Ostreocin-D, discovered in the past decade, is a marine toxin produced by dinoflagellates. It shares structure with palytoxin, a toxic compound responsible for the seafood intoxication named clupeotoxism. At the cellular level, the action sites and pharmacological effects for ostreocin-D are still almost unknown. Previously, we demonstrated that these toxins change the filamentous actin cytoskeleton, which is essential for multiple cellular functions. However, nothing has yet been reported about what happens with the unpolymerized actin pool. Here (i) the effects induced by ostreocin-D on unpolymerized actin, (ii) the Ca2+ role in such a process, and (iii) the cytotoxic activity of ostreocin-D on the human neuroblastoma BE(2)-M17 cell line are shown for the first time. Fluorescently labeled DNase I was used for staining of monomeric actin prior to detection with both laser-scanning cytometry and confocal microscopy techniques. Cellular viability was tested through a microplate metabolic activity assay. Ostreocin-D elicited a rearrangement of monomeric actin toward the nuclear region. This event was not accompanied by changes in its content. In addition, the presence or absence of external Ca2+ did not change these results. This toxin was also found to cause a decrease in the viability of neuroblastoma cells, which was inhibited by the specific blocker of Na+/K+-ATPase, ouabain. All these responses were comparable to those obtained with palytoxin under identical conditions. The data suggest that ostreocin-D modulates the unassembled actin pool, activating signal transduction pathways not related to Ca2+ influx in the same way as palytoxin.
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PMID:Ostreocin-D impact on globular actin of intact cells. 1915 8

An amphiphilic peptide with a 3-arginine stretch and a 6-valine stretch (R3V6) has been previously reported to deliver plasmid DNA (pDNA) into cells with no toxicity. Here, the vascular endothelial growth factor receptor binding peptide (VRBP) was linked to R3V6 to promote endothelial-specific gene delivery. The pDNA/VRBP-linked R3V6 (VRBP-R3V6) complex was physically characterized via various methods. In a gel retardation assay, pDNA was completely retarded by VRBP-R3V6 at a weight ratio of 1:2 (pDNA:peptide). VRBP-R3V6 also protected pDNA from DNase I for longer than 60 min. Heparin competition assay showed that the pDNA/VRBP-R3V6 complex did not release pDNA when heparin was introduced at a two-fold weight excess of pDNA. In vitro transfection showed that VRBP-R3V6 had transfection efficiency into endothelial cells approximately 200 times greater than that of R3V6. In addition, the transfection efficiency was further enhanced into hypoxic endothelial cells. However, in human embryonic kidney 293 and neuroblastoma N2A cells, VRBP-R3V6 only achieved a transfection rate 10 times higher than R3V6, indicating that VRBP-R3V6 has high specificity for endothelial cells. VRBP-R3V6 was also shown to be nontoxic in a cytotoxicity assay. The data presented here suggest that VRBP-R3V6 may prove useful for specific gene delivery to endothelial cells.
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PMID:VEGF receptor binding peptide-linked amphiphilic peptide with arginines and valines for endothelial cell-specific gene delivery. 2268 93


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