Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue transglutaminase (tTG) is a transamidating enzyme that is elevated in Huntington's disease (HD) brain and may be involved in the etiology of the disease. Further, there is evidence of impaired mitochondrial function in HD. Therefore, in this study, we examined the effects of mitochondrial dysfunction on the transamidating activity of tTG. Neuroblastoma SH-SY5Y cells stably overexpressing human tTG or mutated inactive tTG were treated with 3-nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase. 3-NP treatment of tTG-expressing cells resulted in a significant increase of TG activity in situ. In vitro measurements demonstrated that 3-NP had no direct effect on tTG activity. However, 3-NP treatment resulted in a significant decrease of the levels of GTP and ATP, two potent inhibitors of the transamidating activity of tTG. No significant changes in the intracellular levels of calcium were observed in 3-NP-treated cells. Treatment with 3-NP in combination with antioxidants significantly reduced the 3-NP-induced increase in in situ TG activity, demonstrating that oxidative stress is a contributing factor to the increase of TG activity. This study demonstrates for the first time that impairment of mitochondrial function significantly increases TG activity in situ, a finding that may have important relevance to the etiology of HD.
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PMID:Impaired mitochondrial function results in increased tissue transglutaminase activity in situ. 1103 84

Neuroblastoma and pheochromocytoma have the same embryonal origin. They originate from neural crest cells, and they usually affect suprarenal glands. The SDHB gene encodes the B subunit of succinate dehydrogenase, a protein implicated in the electron transport chain and Krebs cycle. Some mutations have been described in this gene in pheochromocytoma, and this gene could be an appropriate candidate for its study in neuroblastoma given its localization in 1p35-36. The aim of this study was to analyze neuroblastoma tumors in order to assess a possible implication of this gene in neuroblastoma development. We studied 28 neuroblastoma tumor samples from different stages. Mutation research in genomic DNA was carried out after individual amplification of each of the eight SDHB exons by SSCP analysis and sequencing of those samples with migration pattern variants. No variant was found except for three polymorphisms in four neuroblastoma samples. The first polymorphism was a synonymous A-->C change in the third position of codon 6 (exon 1). The other two polymorphisms were a TTC insert at the 5' flanking intron sequence of exon 5 in a stretch of seven TTC repeats. Upon the basis of posterior microsatellite instability and hypermethylation promoter studies, which were not significant, we can conclude that the SDHB gene, a positional candidate gene, is unlikely to be related to either initiation or tumoral progression in neuroblastoma.
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PMID:There is no evidence that the SDHB gene is involved in neuroblastoma development. 1649 57

In order to compare the effects of cocaine at morphological, basal cytotoxicity, biochemical and molecular levels, cultured mouse neuroblastoma cells (Neuro-2a) were exposed to a range of concentrations of cocaine hydrochloride. Neuroblastoma cell proliferation, evaluated by quantification of total protein content, was very sensitive to cocaine, being increasingly inhibited from 12 to 72 hr of exposure (EC(50) = 3.1 mm at 24 hr). Cytoplasmic membrane permeability to lactate dehydrogenase was not particularly increased and lysosomal function was stimulated from 0.05 to 1.5 mm, and inhibited from 2.5 mm. A shift to anaerobiosis was detected as intracellular lactate dehydrogenase (LDH) activity was increased and mitochondrial succinate dehydrogenase (SDH) activity decreased. Hexosaminidase (HEX), a lysosomal enzyme involved in sphingolipid degradation, was stimulated only at 1 mm and neural acetylcholinesterase (AChE) activity was stimulated from 2.5 mm. Morphological examination of exposed cultures revealed that most cells became bipolar and multipolar neurons by extension of neurites, but also suffered cytoplasmic vacuolization, hydropic degeneration and nuclear pyknosis. Although cells developing apoptosis were observed, no DNA oligonucleosomal fragmentation was detected by agarose gel electrophoresis of DNA from cells exposed to cocaine. In conclusion, in addition to predominance of anaerobiosis, little disruption of membranes and severe morphologic injury, biochemical and morphological differentiation-like effects were the most prominent alterations produced by cocaine on mouse neuroblastoma cells.
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PMID:Morphological, biochemical and molecular effects of cocaine on mouse neuroblastoma cells culture in vitro. 2065 45