Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ventral lateral geniculate nucleus (vLGN) of the tree shrew (Tupaia belangeri) was differentiated into multiple subdivisions (dorsal cap, intergeniculate leaflet, parvicellular segment, and internal and external magnocellular laminae, the latter being further divisible into a lateral and medial division) on the basis of retinal projections, immunochemistry, and histochemistry. Retinal projections traced with intravitreal injections of wheat germ agglutinin conjugated horseradish peroxidase revealed direct bilateral input to all subregions of the vLGN, except for the internal magnocellular lamina (which received only contralateral input) and the parvicellular segment (which was not retinorecipient). Furthermore, retinal inputs clearly distinguished the relatively heavily retinorecipient intergeniculate leaflet from the less prominently labeled dorsal cap. Immunohistochemical localization of Neuropeptide Y (NPY) perikarya revealed their prominence in the intergeniculate leaflet and the external magnocellular laminae with a concentration along the optic tract. NPY immunoreactive fibers were seen in all but the parvicellular subregion. Gamma amino butyric acid immunoreactivity was seen throughout the vLGN, but was most concentrated in the dorsal cap and the magnocellular laminae, followed by the intergeniculate leaflet. Histochemical studies of cytochrome oxidase and nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase localization revealed similar patterns of dense reactivity within the external magnocellular lamina, intergeniculate leaflet and dorsal cap, and somewhat less dense, but substantial reactivity in the internal magnocellular lamina. Within the external magnocellular lamina, cells reactive for cytochrome oxidase were noted in the lateral portion bordering the optic tract, whereas those specific for NADPH-diaphorase were dispersed throughout the lamina. Poor reactivity for both histochemical markers was evident in the parvicellular segment. Overall, the markedly different patterns of retinal input and neurochemical organization between the subdivisions of the tree shrew vLGN suggest their involvement in diverse functions. Furthermore, the basic similarity of the organization of the tree shrew vLGN to that of the taxonomically unrelated ground squirrel may indicate a common mammalian scheme.
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PMID:Immunohistochemical organization of the ventral lateral geniculate nucleus in the tree shrew. 131 86

Nitric oxide (NO) mediates cell-cell signalling in the brain and stimulates cyclic GMP (cGMP) production in target cells. We have used NADPH-diaphorase (reduced nicotinamide adenine dinucleotide phosphate-diaphorase) histochemistry to identify NO-producing neurones and cGMP immunohistochemistry to locate the targets of NO in rat cerebellum. NADPH-diaphorase staining was prominent in granule cells and in the molecular layer. cGMP immunostaining in cerebellar slices stimulated with the NO donors, nitroprusside and SIN-1, was found in granule cells, glomeruli, fibres, Bergmann glia and in other astrocytes. The results provide visible evidence that NO mediates neuron-neuron and neuron-glia communication.
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PMID:Sources and targets of nitric oxide in rat cerebellum. 131 90

In vitro alterations induced by a 10 micrograms/ml and 50 micrograms/ml dose each of thiophenate and fenbendazole on the absorptive surfaces of Haemonchus contortus (Nematoda: Trichostrongylidae) were studied. The most significant changes were induced in the gut epithelium. Alkaline phosphatase and adenosine triphosphatase activities were decreased, succinic dehydrogenase activity was increased, while acid phosphatase and glucose-6-phosphatase were completely lost from the intestinal epithelium after treatment with either of the drugs. A stimulatory effect of these two anthelmintics was observe on lactic dehydrogenase and reduced nicotinamide adenine dinucleotide diaphorase distribution. Thiophenate caused an increase in the activities of glutamate dehydrogenase (GDH), glucose-6-phosphate dehydrogenase (G-6-PD) and nonspecific esterases and a decrease in reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-D) activity. Fenbendazole treatment led to the inhibition of GDH, while G-6-PD, NADPH-D, cytochrome oxidase, monoamine oxidase and nonspecific esterase activity remained unaltered in the epithelium.
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PMID:Histoenzymic effects of thiophenate and fenbendazole on the absorptive surfaces of Haemonchus contortus. 133 82

The level of expression of mRNAs encoding somatostatin and two isoforms of glutamic acid decarboxylase (Mr 65,000, GAD65 and 67,000, GAD67) was examined by quantitative in situ hybridization histochemistry in the striatum of adult rats after local injections of quinolinic acid. After a 2-week survival period, Nissl strains showed a profound loss of neurons in the injected striata. With a dose of 120 nmol quinolinic acid, the lesioned area was completely devoid of somatostatin mRNA-positive neurons but contained cells expressing nicotinamide adenine dinucleotide-diaphorase activity (a marker of somatostatinergic interneurons in striatum). After 60 nmol of quinolinic acid, the number of neurons expressing somatostatin mRNA in the lesioned area was similar to controls but the level of labeling per neuron was increased. In the lesioned area, labeling for GAD65 mRNA was abolished and labeling for GAD67 mRNA markedly reduced. However, scattered neurons expressing GAD67 mRNA could still be detected. The majority of surviving GABA-ergic neurons expressed immunoreactivity to parvalbumin, a marker for striatal GABA-ergic interneurons. The results show that quinolinic acid induces dose-dependent alterations in the expression of striatal somatostatin mRNA and reveal a relative sparing of GABA-ergic interneurons in the quinolinic acid-lesioned rat striatum.
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PMID:Effects of quinolinic acid on messenger RNAs encoding somatostatin and glutamic acid decarboxylases in the striatum of adult rats. 134 22

Thirty years ago, Thomas and Pearse discovered what they termed 'solitary active cells'--neurons containing an unusually high nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) activity that could be detected histochemically. Although these neurons were considered as something special, an appropriate mechanism to account for their outstanding metabolism was not provided until the recent identification of neuronal NADPH-diaphorase as nitric oxide synthase. This simple histochemical method now allows the precise anatomical localization of the neurons generating the exotic messenger molecule nitric oxide. This article reviews the functional implications that arise from our new knowledge of the anatomy of the nitric oxide signal transduction pathway in the nervous system. The widespread distribution of this system indicates that for those interested in cellular communication nitric oxide is a gas to study.
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PMID:Neurons that say NO. 137 18

The distribution and colocalization of nitric oxide synthase (NOS) and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was studied in the neuronal elements of the adrenal gland of the rat. Ganglion cells and many nerve fibres in the gland showed both NOS-immunoreactivity and NADPH-diaphorase staining. The adrenal cortical cells showed NADPH-diaphorase staining but were not immunoreactive for NOS. Positive labelling for both NADPH-diaphorase and NOS was found in bundles and in single fibres with varicosities, preferentially located around the noradrenaline (NA)-storing cells. Adrenaline (A)-storing cells and ganglion cells in the medulla, along with the cortical cells and blood vessels in the zona glomerulosa, received relatively fewer positive fibres.
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PMID:Colocalization of nitric oxide synthase and NADPH-diaphorase in rat adrenal gland. 138 64

The enzyme DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2) is unusual in that it can utilize either NADH or NADPH as a co-factor for the reduction of its substrates. We have shown that the intact NAD(P)H molecule is not required and that other reduced pyridinium compounds can also act as co-factors for DT diaphorase. The entire adenine dinucleotide portion of NAD(P)H can be dispensed with entirely and the simplest quaternary (and therefore reducible) derivative of nicotinamide, 1-methylnicotinamide, was as effective as NAD(P)H as a co-factor for the reduction of the quinone, menadione. Nicotinamide 5'-O-benzoyl riboside was also as effective a co-factor as NAD(P)H, whilst nicotinamide ribotide and riboside have a higher Km, and decreased the kcat of DT diaphorase. Nicotinic acid derivatives had little activity. Kinetic analysis indicated that both nicotinamide ribotide and riboside may be interacting with the menadione binding site rather than the NAD(P)H site. Irrespective of the differences between the various reduced pyridinium derivatives in their ability to act as co-factors for the reduction of menadione by DT diaphorase, all the compounds that showed activity in this assay were equally effective co-factors for the reduction of the nitrobenzamide, CB 1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide). The apparent Km of DT diaphorase for all these co-factors approached zero. It was concluded that co-factor binding is not a rate-limiting step in the nitroreductase activity of DT diaphorase.
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PMID:Identification of novel reduced pyridinium derivatives as synthetic co-factors for the enzyme DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2). 138 52

NADH was metabolized both by serum components and at the cell surface. The metabolism by serum was either oxidation to NAD+, or hydrolysis of the pyrophosphate to yield nicotinamide mononucleotide (reduced) (NMNH) and AMP. NMNH was further hydrolysed to yield nicotinamide riboside (reduced) (NRH), which was stable. NAD+ was hydrolysed (although at a slower rate than was NADH), but was also reduced to yield NADH. The reduction of NAD+ was catalysed by the enzyme serum L(+)lactate dehydrogenase (EC 1.1.1.27) and was dependent on the concentration of L(+)lactate in the serum. NADPH was hydrolysed in a similar manner to NADH but not oxidized by serum. NADH generated from NAD+ by serum derived from human, foetal calf and horse sources was capable of driving the bioreductive activation of CB 1954 by the enzyme DT diaphorase. Cell surfaces oxidized NADH to NAD+, but did not oxidize NADPH or NRH. These observations suggest that NAD(P)H would be unsuitable as a source of reducing equivalents for the bioreductive activation of prodrugs by a reductase enzyme in Antibody Directed Enzyme Prodrug Therapy (ADEPT). In contrast, NAD+ (which could act as a source of NADH) and NRH could avoid the shortcomings of NAD(P)H, and act as suitable cofactors for an enzyme in an ADEPT system.
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PMID:Metabolism of NAD(P)H by blood components. Relevance to bioreductively activated prodrugs in a targeted enzyme therapy system. 138 14

We have studied the laminar distribution of reduced nicotinamide dinucleotide phosphate diaphorase (NADPH-d) activity and the morphology of positive neurons in the superior colliculus (SC) and the underlying periaqueductal gray (PAG) of the rat. The morphology of NADPH-d-positive neurons has been compared to that of Golgi-impregnated cells. The highest activity occurs in the stratum zonale and stratum griseum superficiale, contrasting with the pale neuropil in the stratum opticum, where only a few positive neurons are found. In the stratum griseum intermedium positive neurons are grouped in patches separated by narrow, NADPH-d-negative bands. In the deeper layers, the neuropil is NADPH-d-negative, and few neurons show enzymatic activity. In contrast, numerous neurons in the dorsolateral part of the PAG are intensely positive. They are continuous with the positive neurons in the stratum album profundum, with no clear border between the two centers. In both SC and PAG, only small and medium sized neurons are NADPH-d-positive. In comparison with Golgi material, all types of small neurons in the superficial layers show NADPH-d activity; NADPH-d histochemistry, however, does not visualize the characteristic dendritic appendages of these neurons. The large neurons of the SC and PAG, probably representing the long-projecting neurons of these centers, do not contain the enzyme.
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PMID:Laminar distribution and morphology of NADPH-diaphorase containing neurons in the superior colliculus and underlying periaqueductal gray of the rat. 141 74

The toxicity of CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] towards human cells was greatly enhanced by NADH (when foetal calf serum was present in the culture medium) and by nicotinamide riboside (reduced) (NRH), but not by nicotinate riboside (reduced). Co-treatment of human cells with CB 1954 and NADH resulted in the formation of crosslinks in their DNA. The toxicity produced by other DNA crosslinking agents was unaffected by reduced nicotinamide compounds. When caffeine was included in the medium, a reduction in the cytotoxicity of CB 1954 occurred. The toxicity experienced by human cell lines after exposure to CB 1954 and NADH was proportional to their levels of the enzyme DT diaphorase NAD(P)H dehydrogenase (quinone), EC 1.6.99.2. It is concluded that NRH, which we have shown to be a co-factor for rat DT diaphorase (Friedlos et al., Biochem Pharmacol 44: 25-31, 1992), is generated from NADH by enzymes in foetal calf serum, and stimulates the activity of human DT diaphorase towards CB 1954.
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PMID:Potentiation of CB 1954 cytotoxicity by reduced pyridine nucleotides in human tumour cells by stimulation of DT diaphorase activity. 144 31


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