Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.5.2 (NQO1)
6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative concentration-toxicity relationships were determined for the injury of cultured murine cortical neurons by several excitatory amino acid (EAA) agonists. All tested agonists produced concentration-dependent neuronal injury at concentrations between 1 and 1000 microM. With 5 min exposure, glutamate, aspartate, N-methyl-D-aspartate (NMDA), L-homocysteate (HCA), and quisqualate all had similar potencies, destroying half of the neuronal population (LD50) at concentrations of 50-200 microM, and similar efficacies, with 88-92% neuronal loss produced by exposure to high agonist concentrations. Quinolinate and kainate were substantially weaker toxins, producing only 20-30% neuronal loss after 5 min exposure to 3 mM concentrations; with prolonged (24 hr) exposure, 85-95% neuronal loss could be attained. The comparative EAA vulnerability of a specific cortical neuronal subpopulation containing high concentrations of the enzyme, reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), was also examined. Glutamate had no differential toxicity on these cells, damaging them at all concentrations in proportion to the general population; however, other, more selective, agonists produced strikingly differential injuries. These NADPH-d-containing [NADPH-d(+)]neurons were selectively resistant to damage by low concentrations of the NMDA agonists quinolinate, HCA, aspartate, or NMDA itself. By contrast, NADPH-d(+)neurons were selectively destroyed by concentrations of quisqualate or kainate too low to produce much general neuronal injury. The differential susceptibility of these neurons was not absolute, as high concentrations of all tested agonists produced nonselective neuronal injury. In light of recent evidence that forebrain NADPH-d(+)neurons are selectively spared in Huntington's disease, the present study continues to support the hypothesis that neuronal loss in Huntington's disease might result from excessive NMDA-receptor stimulation by any selective NMDA agonist. Furthermore, the demonstration that the differential susceptibility of NADPH-d(+)neurons is agonist concentration-dependent, rather than absolute, could provide a basis for explaining some existing conflicting experimental data.
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PMID:Vulnerability of cultured cortical neurons to damage by excitotoxins: differential susceptibility of neurons containing NADPH-diaphorase. 338 92

Recent studies have suggested that large amounts of free zinc may be coreleased during excitatory synaptic transmission at glutamatergic synapses, and may act postsynaptically to decrease actions mediated by N-methyl-D-aspartate (NMDA) receptors, while often increasing neuroexcitation mediated by quisqualate receptors. The present study examined the ability of zinc to alter excitatory amino acid (EAA) neurotoxicity. Murine cortical cell cultures were exposed to EAAs for 5 min in defined solutions, and neuronal cell injury was examined the following day both morphologically and by lactate dehydrogenase assay. Inclusion of 30-500 microM zinc in the exposure solution produced a zinc concentration-dependent, noncompetitive attenuation of NMDA-induced neuronal injury, with an ED50 of about 80 microM. In contrast, zinc produced the same concentration-dependent potentiation of quisqualate neurotoxicity; and with 500 microM zinc, a small potentiation of kainate neurotoxicity was suggested. The effect of zinc on the neurotoxicity of the broad-spectrum agonist glutamate was consistent with these effects on specific agonists, as well as with a previous study showing that glutamate neurotoxicity normally depends predominantly on NMDA-receptor activation. Zinc produced a concentration-dependent reduction in glutamate-induced neuronal injury in a fashion similar to that seen with NMDA, but less effectively. In addition, despite this overall protective effect, zinc paradoxically increased the glutamate-induced destruction of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d)-containing neurons, a subpopulation that was shown in the preceding paper (Koh and Choi, 1988) to exhibit resistance to NMDA receptor-mediated neurotoxicity, and vulnerability to non-NMDA receptor-mediated neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Zinc alters excitatory amino acid neurotoxicity on cortical neurons. 338 93

The ultrastructure of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive neurons in cat cerebral cortex, amygdala and caudate nucleus was investigated by electron microscopy using a modified method applicable to aldehyde-fixed tissues. These NADPH diaphorase-positive neurons were morphologically similar to neurons immunohistochemically positive for somatostatin. They had large amounts of electron-dense formazan reaction products scattered through the whole cytoplasm but not in the mitochondria or nucleus. Similar electron-dense reaction products were visible in the dendrites of these neurons. The results indicate that NADPH diaphorase histochemistry is a useful method for the ultrastructural examination of particular groups of neurons.
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PMID:Ultrastructure of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive neurons in the cat cerebral cortex, amygdala and caudate nucleus. 340 36

Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase), which is specifically localized in neurons, has been histochemically demonstrated in human brain by using a perfusion-fixation procedure. With such fixed human brainstem, it was possible to study the topographic organization of NADPH-diaphorase-containing neurons that were visualized in fine detail for the first time. In the pontomesencephalic region, positive neurons were observed in nuclei around the decussation and arm of the superior cerebellar peduncle. These nuclei included the pedunculopontine tegmental, lateral parabrachial and oral pontine reticular nuclei. The positive somata were mainly multipolar in shape and medium to large in size. The positive neurons appeared to correspond to cholinergic neurons, at least partly in the brainstem, in terms of both the patterns of distribution and the cellular morphology.
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PMID:Reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry in the pontomesencephalic region of the human brainstem. 341 79

The purpose of this study was to evaluate the effect of endurance exercise on the histochemistry and wet weight of the reinnervating rat plantaris muscle. Two groups of young female Wistar rats (6 weeks old), 1 sedentary denervated control (n = 13) and 1 exercised denervated experimental (n = 17), were denervated unilaterally by cutting and resecting the sciatic nerve. To effect reinnervation a skin grafting operation was carried out on the nerve so that the gap caused by resection was bridged. The third group was the sedentary non-denervated normal control (n = 10). A progressive training program of 18 weeks of treadmill running was carried out by the experimental group. Approximately 5 months after denervation, the plantaris muscles were studied histochemically for reduced nicotinamide adenine dinucleotide diaphorase (NADH-D) and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activities. Fibres were classified as "red", "white", or "intermediate" with NADH-D. Alpha-GPD differentiates "intermediate" from "red" fibre types in case of difficulty in differentiating these fibre types from each other with NADH-D. The weight of the reinnervated plantaris muscle increased significantly after exercise. The exercise did not change the fibre type proportions--including "red" fibre type--in the deep region of the reinnervating plantaris. There were significant differences between normal control and denervated control or experimental groups in histochemical fibre populations in the deep region of the plantaris. The findings of this study suggest that: treadmill running did not increase the oxidative capacity of the deep region of the reinnervating rat plantaris muscle; treadmill training did not damage the reinnervating plantaris.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of endurance exercise on fibre type composition and muscle weight of reinnervating rat plantaris muscle. 358 51

The substantia innominata encompasses an area of the basal forebrain that is ventral to the lenticular nucleus and anterior commissure, medial to the claustrum and external capsule, and lateral to the hypothalamus. The nucleus basalis of Meynert consists primarily of large acetylcholinesterase (AchE)-positive neurons embedded within the substantia innominata. Damage to these neurons may be important in the pathogenesis of cortical dysfunction in Alzheimer's disease. In order to characterize other neuronal elements in the substantia innominata and their relationship to the nucleus basalis, we chose to study a biochemically distinct neuronal subset containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). The substantia innominata was blocked from six normal brains obtained postmortem and fixed in neutral-buffered formalin at 4 degrees C for 48 hours. Free-floating 50-micron sections from several levels were stained for NADPH-d or AchE activities. Selected sections were double stained for NADPH-d and AchE. NADPH-d activity was present in a network of pleomorphic neurons that extended through all levels of the substantia innominata and into the striatum and amygdala. NADPH-d neurons were particularly numerous at the level of the anterior commisure and were closely associated with the cholinergic neurons of the nucleus basalis. They were not seen in the ventral pallidum, or the vertical limb of the diagonal band of Broca or in the islands of Calleja. The cell bodies of NADPH-d neurons were quite varied in shape, ranging from ovoid to fusiform, and about half the cells were bipolar. Where neuronal density was high, their dendrites formed an interlacing pattern. NADPH-d-positive fibres were seen coursing through the external capsule, hypothalamus, and amygdala. This novel set of neurons in the substantia innominata may be part of a more extensive network that interacts with the magnocellular basal forebrain system at the level of the nucleus basalis. Whether other neurotransmitters are present within these neurons and whether NADPH-d neurons are involved in Alzheimer's disease remain to be elucidated.
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PMID:Subset of neurons characterized by the presence of NADPH-diaphorase in human substantia innominata. 361 5

This work tested whether the membrane electrical properties of cat motoneurons, the contractile properties of their muscle units, and the normal relationships among them would be restored 9 mo after section and resuture of their muscle nerve. Properties of medial gastrocnemius (MG) motor units were examined 9 mo following section and resuture of the MG nerve in adult cats. Motoneuron electrical properties and muscle-unit contractile properties were measured. Motor units were classified on the basis of their contractile properties as type fast twitch, fast fatiguing (FF), fast twitch with intermediate fatigue resistance (FI), fast twitch, fatigue resistant (FR), or slow twitch, fatigue resistant (S) (8, 20). Muscle fibers were classified as type fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow oxidative (SO) on the basis of histochemical staining for myosin adenosine triphosphatase, nicotinamide adenine dinucleotide diaphorase, and alpha-glycerophosphate dehydrogenase (48). Following 9 mo self-reinnervation, the proportions of each motor-unit type were the same as in normal control animals. Motoneuron membrane electrical properties [axonal conduction velocity, afterhyperpolarization (AHP) half-decay time, rheobase, and input resistance] also returned to control levels in those motoneurons that made functional reconnection with the muscle (as determined by ability to elicit measurable tension). The relationships among motoneuron electrical properties were normal in motoneurons making functional reconnection. Approximately 10% of MG motoneurons sampled did not elicit muscle contraction. These cells' membrane electrical properties were different from those that did elicit muscle contraction. Contractile speed and fatigue resistance of reinnervated muscle units had recovered to control levels at 9 mo postoperation. Force generation did not recover fully in type-FF units. The reduced tensions were apparently due to failure of recovery of FG muscle fiber area. Following reinnervation, relationships between motoneuron electrical and muscle-unit contractile properties were similar to controls. This was reflected in a degree of correspondence between motor-unit type and motoneuron type similar to normal units (84 vs. 86%, as defined by Ref. 61). There was a significantly increased proportion of type-SO muscle fibers and a decrease in the fast muscle fibers (especially type FOG) in 9 mo reinnervated MG. Together with the unchanged proportions of motor-unit types, this led to an estimate of average innervation ratios being increased in type-S motor units and decreased in type-FR units.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Properties of self-reinnervated motor units of medial gastrocnemius of cat. I. Long-term reinnervation. 371 73

The individual effects of two putative metabolites of primaquine (5,6-dihydroxyprimaquine and 5,6-dihydroxy-8-aminoquinoline) on the hexose monophosphate shunt (HMS) and on the ATP-dependent proteolytic system which rapidly degrades oxidized erythrocyte protein were measured in intact red blood cells in vitro from two blood donors. In red cells treated with nitrite (1-40 mM) or phenylhydrazine (0.01-10 mM), proteolytic activity was detected only with concentrations (7.5 mM NaNO2 and 0.25 mM phenylhydrazine) causing greater than 15-fold elevation of HMS activity, and glucose-6-phosphate dehydrogenase (G6PD)-deficient (25% of normal activity) red cell suspensions thus treated showed approximately 30% greater proteolysis. G6PD-normal and deficient red cells treated with the primaquine analogs, however, did not experience proteolysis with concentrations (0.25 mM) in excess of those causing 17-fold elevation of HMS activity. Stimulation of the HMS by the primaquine analogs thus appears unrelated to an erythrotoxic oxidative stress. Methylene blue is known to cause an elevation of HMS activity through direct and diaphorase II-dependent oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) which is independent of injurious oxidative stress. It was found that the putative primaquine metabolites also caused direct and diaphorase II-dependent oxidation of NADPH in dilute hemolysate, thus suggesting that the putative primaquine metabolites have a methylene blue-like redox disposition in red blood cells. Results obtained in this study suggest that the hemolytic toxicity of primaquine may be unrelated to processes which lead to oxidative deterioration of red cell protein.
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PMID:Oxidative activity of hydroxylated primaquine analogs. Non-toxicity to glucose-6-phosphate dehydrogenase-deficient human red blood cells in vitro. 375 45

In the intermediate layers of the rat and mouse colliculus there is a lattice-like pattern of high nicotinamide adenine dinucleotide phosphate diaphorase activity. This lattice is composed of dark bands that are 100-200 micron wide and enclose pale areas of irregular shape. A very similar lattice of high acetylcholinesterase activity is also found in the intermediate layers and this overlaps the diaphorase lattice almost completely. However, in deeper layers the enzymes have a complementary organization with high levels of one being associated with low levels of the other. It is concluded that the histochemical lattices will provide useful patterns with which to compare the terminal organization of afferent systems.
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PMID:Spatial relationship of NADPH-diaphorase and acetylcholinesterase lattices in the rat and mouse superior colliculus. 377 47

The activity of reduced nicotinamide adenine dinucleotide (NADH)-diaphorase was examined histochemically in the amygdala, cortex and sublenticular substantia innominata (nucleus basalis of Meynert) of patients with Alzheimer's disease and senile dementia of the Alzheimer type (SDAT). Senile plaques were characterized by increased enzyme levels and the presence of astrocytes highly reactive for NADH-diaphorase. In the sublenticular substantia innominata, the number of neurons positive for NADH-diaphorase was reduced in both Alzheimer's disease and SDAT, a result paralleled by a reduction of Nissl-stained cells, and this pathology was accompanied by an increase in the number of astrocytes. Intact substantia innominata somata in the former dementia, however, showed essentially normal levels of the enzyme, whereas in the SDAT patients, an abnormal distribution of NADH-diaphorase was observed frequently. It is proposed that the increased NADH-diaphorase associated with senile plaques and their accompanying astrocytes may be linked, in part, to the increased astrogliosis and decrease of neurons in the basal forebrain and that neuropathologic differences may exist between Alzheimer's disease and SDAT in terms of energy metabolism.
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PMID:Alzheimer dementia and reduced nicotinamide adenine dinucleotide (NADH)-diaphorase activity in senile plaques and the basal forebrain. 383 7


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