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

---

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.
...
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)
...
PMID:Zinc alters excitatory amino acid neurotoxicity on cortical neurons. 338 93

The recent discovery of the identify of nitric oxide synthase with the reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) has powerfully stimulated the anatomical localization of sites of nitric oxide synthesis in the nervous system. In the present study the widely used light microscopical technique for NADPH-d staining was adapted to the electron microscopical level by applying the tetrazolium salt 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl)tetrazolium chloride (BSPT) which produces an electron-dense reaction product, BSPT-formazan. Predominantly membranes of the endoplasmic reticulum were stained. Apart from singular heavily labeled neurons, a majority of nerve cells, light microscopically "unstained", shows sporadically formazan deposits, and, likewise, but regionally different, a few astroglial cells. Lesions induced by the glutamate agonists quinolinic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) display surviving neurons, which are predominantly stained for NADPH-d. Astroglial cells within lesioned areas exhibit increased amounts of reaction product, apparently as a consequence of enzyme induction.
...
PMID:Nitric oxide synthase in the brain: light and electron microscopical findings based on the NADPH-diaphorase reaction. 753 22

The distribution of nitric oxide producing neurones in the medulla oblongata of the cat was investigated using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, and nitric oxide synthase (NOS) immunohistochemistry. The pattern of staining obtained with both methods was found to be similar. Strongly diaphorase and NOS reactive neurones were present in the paramedian and lateral tegmental fields, including the regions occupied by the A1/C1 catecholamine cell groups, the nucleus ambiguus and lateral reticular nucleus, and in a number of sensory nuclei including the nucleus of the tractus solitarius and the dorsal column nuclei. The extent of co-localization of NADPH-diaphorase with a number of neuropeptides and neurotransmitters was investigated by combining NADPH-diaphorase histochemistry with immunocytochemistry for neuropeptide Y, somatostatin, glutamate, cholecystokinin and tyrosine hydroxylase. NADPH-diaphorase reaction product was observed in neurones immunoreactive for glutamate and somatostatin. These double-labelled cells were found in the paramedian region, lateral reticular field, the nucleus prepositus hypoglossi and in the rostral nucleus of the tractus solitarius. In the rostral ventrolateral medulla NADPH-diaphorase/somatostatin immunoreactive cells were found in the paragigantocellular nucleus. NADPH-diaphorase/glutamate immunoreactive cells overlapped the nucleus ambiguus, the lateral reticular nucleus and the A1/C1 catecholaminergic cell groups. In addition, a few NADPH-diaphorase/glutamate immunoreactive cells were found in the paraolivary area and gigantocellular tegmental field, in the external cuneate and infratrigeminal nuclei. The functional implications of the co-localization of nitric oxide with these neurotransmitters in areas of the medulla concerned with cardiovascular regulation is discussed.
...
PMID:Co-localization of neurotransmitter immunoreactivities in putative nitric oxide synthesizing neurones of the cat brain stem. 754 Dec 9

Change in cytosolic calcium ion level ([Ca2+]) after glutamate exposure was evaluated using fluo-3 on rat cortical neurons. The result showed that neurons that contain nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) were capable of blocking glutamate-induced rise in [Ca2+]. However, with the inhibitor of nitric oxide synthase, NADPH-d-positive cells lost their ability to regulate [Ca2+], suggesting a possible role of nitric oxide in protecting this distinct class of neurons from glutamate neurotoxicity by inhibiting glutamate-induced calcium influx.
...
PMID:Endogenous nitric oxide blocks calcium influx induced by glutamate in neurons containing NADPH diaphorase. 769 7

The topographical relationships between cholinergic neurons, identified by their immunoreactivity for choline acetyltransferase (ChAT) or their staining for beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, and dopaminergic, serotoninergic, noradrenergic, and glutamatergic neurons that occur in the mesopontine tegmentum, were studied in the squirrel monkey (Saimiri sciureus). The ChAT-positive neurons in the pedunculopontine nucleus (PPN) form two distinct subpopulations, one that corresponds to PPN pars compacta (PPNc) and the other to PPN pars dissipata (PPNd). The ChAT-positive neurons in PPNc are clustered along the dorsolateral border of the superior cerebellar peduncle (SP) at trochlear nucleus levels, whereas those in PPNd are scattered along the SP from midmesencephalic to midpontine levels. At levels caudal to the trochlear nucleus, ChAT-positive neurons corresponding to the laterodorsal tegmental nucleus (LDT) lie within the periaqueductal gray and extend caudally as far as locus coeruleus levels. All ChAT-positive neurons in PPN and LDT stain for NADPH-diaphorase; the majority of large neurons in PPN and LDT are cholinergic, but some large neurons devoid of NADPH-diaphorase also occur in these nuclei. Cholinergic neurons in the mesopontine tegmentum form clusters that are largely segregated from raphe serotonin-immunoreactive neurons, as well as from nigral dopaminergic and coeruleal noradrenergic neurons, as revealed by tyrosine hydroxylase immunohistochemistry. Nevertheless, dendrites of cholinergic and noradrenergic neurons are closely intermingled, suggesting the possibility of dendrodendritic contacts. In addition, numerous large and medium-sized glutamate-immunoreactive neurons are intermingled among cholinergic neurons in PPN. Furthermore, at trochlear nucleus levels, about 40% of cholinergic neurons display glutamate immunoreactivity, whereas other neurons express glutamate or ChAT immunoreactivity only. This study demonstrates that 1) cholinergic neurons remain largely segregated from monoaminergic neurons throughout the mesopontine tegmentum and 2) PPN contains cholinergic and glutamatergic neurons as well as neurons coexpressing ChAT and glutamate in primates.
...
PMID:Pedunculopontine nucleus in the squirrel monkey: distribution of cholinergic and monoaminergic neurons in the mesopontine tegmentum with evidence for the presence of glutamate in cholinergic neurons. 791 26

To demonstrate the regional, cellular and subcellular distributions of non-N-methyl-D-aspartate glutamate receptors in rat brain, we generated antipeptide antibodies that recognize the C-terminal domains of individual subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring glutamate receptors (i.e. GluR1, GluR4, and a region highly conserved in GluR2, GluR3 and GluR4c). On immunoblots, antibodies detect distinct proteins with mol. wts ranging from 102,000 to 108,000 in homogenates of rat brain. Immunocytochemistry shows that glutamate receptor subunits are distributed abundantly and differentially within neuronal cell bodies and processes in cerebral cortex, basal ganglia, limbic system, thalamus, cerebellum and brainstem. The precise patterns and cellular localizations of glutamate receptor subunit immunoreactivities are unique for each antibody. In neocortex and hippocampus, pyramidal neurons express GluR1 and GluR2/3/4c immunoreactivities; many non-pyramidal, calcium-binding, protein-enriched neurons in cerebral cortex are selectively immunoreactive for GluR1. In striatum, the cellular localizations of GluR1, GluR2/3/4c and GluR4 immunoreactivities are different; in this region, GluR1 co-localizes with many cholinergic neurons but is only present in a minor proportion of nicotinamide adenine dinucleotide phosphate diaphorase-positive striatal neurons. GluR1 co-localizes with most dopaminergic neurons within the substantia nigra. In several brain regions, astrocytes show GluR4 immunoreactivity. Within the cerebellar cortex, cell bodies and processes of Bergmann glia express intense GluR4 and GluR1 immunoreactivities; perikarya and dendrites of Purkinje cells show GluR2/3/4c immunoreactivity but no evidence of GluR1 or GluR4. Ultrastructurally, GluR subunit immunoreactivities are localized within cell bodies, dendrites and dendritic spines of specific subsets of neurons and, in the case of GluR1 and GluR4, in some populations of astrocytes. This investigation demonstrates that individual AMPA-preferring glutamate receptor subunits are distributed differentially in the brain and suggests that specific neurons and glial cells selectively express glutamate receptors composed of different subunit combinations. Thus, the co-expression of all AMPA receptor subunits within individual cells may not be obligatory for the functions of this glutamate receptor in vivo.
...
PMID:AMPA glutamate receptor subunits are differentially distributed in rat brain. 838 83

Tegmental cholinergic neurons vary their discharge patterns across the sleep-wake cycle, and glutamate is suggested to play an important role in determining these firing patterns. Cholinergic and noncholinergic neurons in the mesopontine tegmentum have different susceptibilities to various excitotoxins, presumably because of heterogeneity in the expression of glutamate receptor subtypes in this area. By using a double-labeling procedure that combines nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) histochemistry and avidin-biotin-peroxidase immunocytochemistry with diaminobenzidine as the chromogen, we compared the colocalization of AMPA receptor subunits GluR1, GluR2/3, and GluR4, kainate receptor subunits GluR5/6/7, and an NMDA receptor subunit NMDAR1 on NADPH-diaphorase-positive (cholinergic) neurons in the mesopontine tegmentum. Throughout the brainstem, neurons immunoreactive for GluR2/3 and NMDAR1 were most numerous, whereas neurons labeled for GluR1, GluR4, and GluR5/6/7 were less common. Specifically within the mesopontine tegmentum, the proportion of double-labeled neurons in the diaphorase-containing cell population was highest with GluR1 (43%) and lowest with GluR5/6/7 (12%). Regardless of the receptor subunit type, the greatest numbers of double-labeled neurons were observed in the pedunculopontine tegmental nucleus pars compacta and the fewest in the dorsal aspect of the laterodorsal tegmental nucleus. In addition, there were regional differences in the relative expression of receptor subunits and diaphorase-positive neurons across the subdivisions of the tegmental cholinergic column. Because each ionotropic subunit confers distinctive properties to a receptor channel, the present results suggest that mesopontine cholinergic neurons have nonuniform responses to glutamate and are also discriminable from basal forebrain cholinergic neurons in terms of glutamate receptor configuration.
...
PMID:Colocalization of ionotropic glutamate receptor subunits with NADPH-diaphorase-containing neurons in the rat mesopontine tegmentum. 872 91

To investigate the role of nitric oxide in the cerebellar degeneration during methylmercury intoxication, interaction of the change in nitric oxide synthase activity and degeneration of the granular layer neurons was examined in rats after methylmercury administration. Both reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and anti-nitric oxide synthase antibody staining, and measurement of glutamate, and nitrite and nitrate levels in the cerebrospinal fluid were performed after oral administration of 5 mg/kg of methylmercury for 12 days. Nitric oxide synthase activity in the cerebellum was also assayed by monitoring the conversion of arginine to citrulline. Methylmercury levels in the blood and the cerebellum gradually increased up to day 13 after the initial methylmercury administration, and neurological disturbances, such as hindleg crossing and abnormal gait, were observed from day 17 after administration. Although a significant decrease in the number of granular layer neurons was recognized at day 84, no such decrease either in NADPH-diaphorase or anti-nitric oxide synthase antibody positive neurons was seen. Glutamate levels in the cerebrospinal fluid transiently increased at day 9 and finally decreased at day 84. Also a transient increase in both nitrite and nitrate levels in the cerebrospinal fluid and nitric oxide synthase activity in the cerebellum was seen prior to the start of degeneration of the granular layer neurons. These results suggest that nitric oxide may play an important role in the degeneration process of the granular layer neurons during methylmercury intoxication.
...
PMID:Role of nitric oxide in the cerebellar degeneration during methylmercury intoxication. 910 26

Nitric oxide may serve as a retrograde messenger to refine or stabilize synapses in the developing nervous system. Whether this action is dependent upon glutamate and the N-methyl-D-aspartate receptor is not yet established. We have used the patch-cluster system in the intermediate gray layer (IGL) of the rat superior colliculus (SC), a system receiving both glutamatergic and cholinergic input, to study this question. The normal distribution and development of nitric oxide synthase (NOS) in SC was examined using nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry in Sprague-Dawley rats aged P4 to adulthood. Fibers containing acetylcholine (ACh) were identified using choline acetyltransferase (ChAT) immunocytochemistry. In addition, N omega-nitro-L-arginine, an inhibitor of NOS, was injected intraperitoneally from birth until P10, P14, P18, or P21-22 to determine if NOS inhibition would disrupt the formation of the ACh patches. Control animals were studied from the same age groups. Our results show NADPH-d-labeled cells within the periaqueductal gray and the deep gray layer of SC by P4, the earliest age examined. By P8-P9, cells in the IGL were well labeled by NADPH-d, while few in the superficial layers (SL) were labeled. SL cells were visible by P10 and were intensely labeled by P14. IGL cells transiently expressed NADPH-d in that the number of labeled cells increased from P8 to P35, then decreased in the adult. ChAT-labeled fibers first appeared in the IGL at P10, formed a characteristic two-tier pattern by P14, and established obvious patches by P21. Inhibition of NOS from birth produced no qualitative differences in the distribution or density of either ChAT-labeled fibers or NADPH-d-labeled cells and fibers at any of the ages examined. We therefore conclude that NO does not contribute to the refinement of cholinergic fiber patches in the rat SC, probably because the fiber system is not glutamatergic.
...
PMID:Inhibition of nitric oxide synthase fails to disrupt the development of cholinergic fiber patches in the rat superior colliculus. 920 10


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---