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)

Studies of motor neurons are difficult because of limitations in their isolation and culture. One solution is to produce clonal neural hybrid cells that can express motor neuron characteristics; we fused an aminopterin-sensitive and neomycin-resistant mouse neuroblastoma cell line to isolated embryonic mouse spinal cord motor neurons. Several hybrid neuron cell lines expressing high levels of choline acetyltransferase (CHAT) enzyme activity were found. These were cloned and clones with high CHAT activity isolated. The hybrid nature of cloned cells was confirmed by karyotyping and determining glucose phosphate isomerase allozymes. The availability of these embryonic clonal hybrid cells will enable molecular, physiological, and biochemical studies to define motor neuron-specific properties.
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PMID:Embryonic mouse spinal cord motor neuron hybrid cells. 175 4

Neuroblastoma cells, cultivated on plastic dishes, in presence of 15 mM glucose resist very well to hypoxia. Cells incubated on plastic dishes, if left unshaken, showed a Pasteur effect at an oxygen concentration below 10%. Oxygen diffusion was the limiting factor in these plastic dishes since improved oxygen diffusion, as a result of shaking, decreased the lactate production considerably at all oxygen concentrations used. When cells were cultivated on Petriperm((R)) dishes, coated with polylysine, oxygen diffusion was no longer a rate-limiting factor: less lactate was produced at 21% O(2) and hypoxia, down to 2.5% O(2) did not show any increase in the rate of lactate production, while Antimycin A drastically increased the glycolytic rate. A situation of limited oxygen availability resulted in two different kinds of adaptation of the neuroblastoma cells: first an instantaneous metabolic regulation leading to an increased glycolytic rate-the Pasteur effect-followed later by an increase in the activities of the glycolytic enzymes-hexokinase (EC 2.7.1.1), phosphoglucose isomerase (EC 5.3.1.9), 6-phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40) and lactate dehydrogenase (EC 1.1.1.27) and a simultaneous decrease of the mitochondrial cytochrome c oxidase (EC 1.9.3.1) activity. However, when the glucose concentration in the medium was decreased to 5 mM the cells were affected by hypoxia already at 5% O(2): cells released lactate dehydrogenase extracellularly and their protein content was decreased. This toxic effect of hypoxia was related to the exhaustion of the glucose supply.
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PMID:Effect of oxygen and glucose availability on the glycolytic rate in neuroblastoma cells under different conditions of culture. 2048 70

Altered glucose metabolism is a hallmark for cancer, which is characterized by a unique metabolic phenotype known as Warburg effect or aerobic glycolysis. Emerging studies show that valproic acid (VPA), an established histone deacetylase inhibitor, possesses tumor suppressive properties. However, the effects of VPA on the regulation of Warburg effect in neuroblastoma (NB), the most common extracranial malignancy in childhood, still remain elusive. In this study, we show that VPA inhibits the aerobic glycolysis in NB cells by decreasing glucose uptake and reducing lactate and ATP production. Mechanistically, VPA suppresses aerobic glycolysis via reducing the levels of E2F transcription factor 1 (E2F1), resulting in repressed expression of glycolytic genes glucose-6-phosphate isomerase (GPI) and phosphoglycerate pinase 1 (PGK1). Rescue experiments show that VPA inhibits the aerobic glycolysis and NB progression through down-regulation of E2F1. These results demonstrate that VPA suppresses the Warburg effect and tumor progression, indicating a novel therapeutic strategy for NB.
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PMID:Valproic acid suppresses Warburg effect and tumor progression in neuroblastoma. 3046 85

Aerobic glycolysis is a hallmark of metabolic reprogramming in tumor progression. However, the mechanisms regulating glycolytic gene expression remain elusive in neuroblastoma (NB), the most common extracranial malignancy in childhood. Herein, we identify that CUT-like homeobox 1 (CUX1) and CUX1-generated circular RNA (circ-CUX1) contribute to aerobic glycolysis and NB progression. Mechanistically, p110 CUX1, a transcription factor generated by proteolytic processing of p200 CUX1, promotes the expression of enolase 1, glucose-6-phosphate isomerase, and phosphoglycerate kinase 1, while circ-CUX1 binds to EWS RNA-binding protein 1 (EWSR1) to facilitate its interaction with MYC-associated zinc finger protein (MAZ), resulting in transactivation of MAZ and transcriptional alteration of CUX1 and other genes associated with tumor progression. Administration of an inhibitory peptide blocking circ-CUX1-EWSR1 interaction or lentivirus mediating circ-CUX1 knockdown suppresses aerobic glycolysis, growth, and aggressiveness of NB cells. In clinical NB cases, CUX1 is an independent prognostic factor for unfavorable outcome, and patients with high circ-CUX1 expression have lower survival probability. These results indicate circ-CUX1/EWSR1/MAZ axis as a therapeutic target for aerobic glycolysis and NB progression.
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PMID:Therapeutic targeting of circ-CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression. 3170 24