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)

Heme oxygenase (HO)-1 and -2 produce carbon monoxide, which is suspected, as is nitric oxide (NO), to function as a neuronal messenger. We report on glucocorticoid-mediated modulation of HO-2 and NO synthase expression in brain and the differential response of the two proteins to corticosterone in different brain regions. Corticosterone treatment (40 mg/kg, 20 days) had opposing effects on HO-2 and NO synthase transcript levels: increasing the 1.3- and 1.9-kb HO-2 mRNAs and decreasing that of the brain-specific 10.5-kb NO synthase. Corticosterone did not uniformly affect HO-2 protein expression in all regions, but appeared to cause a universal reduction in NO synthase, e.g., HO-2 was decreased in hippocampus (CA1 and dentate gyrus), but not in cerebellum. In contrast, NADPH diaphorase staining was reduced in hippocampus and in molecular and granule layers of cerebellum (not detected in Purkinje cells). Striking deficits in neuronal morphology and number of diaphorase-staining neurons were observed in the lateral tegmental area, paraventricular nucleus, and frontal cortex; HO-2 expression was only selectively affected. In cerebellum, activity of NO synthase, but not that of HO, was reduced. Consistent with the possibility that carbon monoxide can generate cyclic GMP, the change in cyclic GMP level did not mirror the decrease in NO synthase. We suggest that glucocorticoid-mediated deficits in hippocampal functions may reflect their negative effect on messenger-generating systems.
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PMID:Corticosterone regulates heme oxygenase-2 and NO synthase transcription and protein expression in rat brain. 751 67

Nitric oxide can act as a neurotransmitter and a retrograde modulator of synaptic transmission, but uncontrolled nitric oxide synthase activity has been associated with neural degeneration. Although earlier studies using immunohistochemistry, in situ hybridization, and NADPH-diaphorase staining had suggested that nitric oxide synthase is not expressed in the CA1 neurons of the hippocampus, we have recently demonstrated that NADPH-diaphorase activity can be detected in CA1 neurons of the hippocampus. To confirm that this diaphorase activity reflects nitric oxide synthase, we have developed a more sensitive in situ hybridization procedure, and an RNase protection assay to detect message for constitutive nitric oxide synthase, the form constitutively expressed in many neurons. Message for constitutive nitric oxide synthase is expressed in the hippocampus, and it is localized to neural cell layers CA1, CA3, the dentate gyrus and some displaced neurons, but not to CA2. Expression of constitutive nitric oxide synthase message in the CA1 region was lost when pyramidal neurons died due to transient forebrain ischemia, supporting the conclusion that CA1 pyramidal cells express constitutive nitric oxide synthase. Although constitutive nitric oxide synthase message is strongly expressed in CA3 and the dentate gyrus, there is little diaphorase activity in these cells, suggesting that there may be post-transcriptional controls that limit constitutive nitric oxide synthase expression in some cells. Message for constitutive nitric oxide synthase is also present in a number of other regions, including the amygdala, several hypothalamic nuclei, the cerebellum, the olfactory bulb, two distinct regions of the perirhinal cortex, the subthalamic nuclei, a neuronal layer in the retrosplenial granular cortex, the lateral geniculate nucleus, the presubiculum, the inferior colliculus, the superior colliculus, the pedunculopontine tegmental nucleus, and scattered individual neurons in the cortex, hippocampus and brainstem. These studies support a role for nitric oxide in multiple regions of the central nervous system. In particular, nitric oxide synthase, the enzyme responsible for the synthesis of nitric oxide, is expressed in the CA1 region of the hippocampus, where there is evidence that nitric oxide may play a major role in long-term potentiation. CA1 hippocampal neurons are an example of a population of neurons that express constitutive nitric oxide synthase but are very sensitive to excitotoxicity and ischemic insults.
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PMID:Expression of the neural form of nitric oxide synthase by CA1 hippocampal neurons and other central nervous system neurons. 753 83

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-stained profiles were evaluated throughout the human hippocampal formation (i.e., dentate gyrus, Ammon's horn, subicular complex, entorhinal cortex) and perirhinal cortex. NADPH-d staining revealed pleomorphic cells, fibers, and blood vessels. Within the entorhinal and the perirhinal cortices, darkly stained (type 1) NADPH-d pyramidal, fusiform, bipolar, and multipolar neurons with extensive dendrites were scattered mainly within deep layers and subjacent white matter. Moderately stained (type 2) NADPH-d round or oval neurons were seen mainly in layers II and III of the entorhinal and perirhinal cortices, in the dentate gyrus polymorphic layer, in the CA fields stratum pyramidal and radiatum, and in the subicular complex. The distribution of type 2 cells was more abundant in the perirhinal cortex compared to the hippocampal formation. Lightly stained (type 3) NADPH-d pyramidal and oval neurons were distributed in CA4, the entorhinal cortex medial subfields, and the amygdalohippocampal transition area. Sections concurrently stained for NADPH-d and nitric oxide synthase (NOS) revealed that all type 1 neurons coexpressed NOS, whereas types 2 and 3 were NOS immunonegative. NADPH-d fibers were heterogeneously distributed within the different regions examined and were frequently in close apposition to reactive blood vessels. The greatest concentration of fibers was in layers III and V-VI of the entorhinal and perirhinal cortices, dentate gyrus polymorphic and molecular layers, and CA1 and CA4. A band of fibers coursing within CA1 divided into dorsal and ventral bundles to reach the presubiculum and entorhinal cortex, respectively. Although the distribution of NADPH-d fibers was conserved across all ages examined (28-98 years), we observed an increase in the density of fiber staining in the aged cases. These results may be relevant to our understanding of selective vulnerability of neuronal systems within the human hippocampal formation in aging and in neurodegenerative diseases.
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PMID:Reduced nicotinamide adenine dinucleotide phosphate-diaphorase/nitric oxide synthase profiles in the human hippocampal formation and perirhinal cortex. 756 Feb 97

Neurons containing nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase exhibit high resistance to several excitotoxins. In the neocortex and striatum, however, these neurons are sensitive to kainic acid. Here we report that, 2 weeks after i.p. injection of kainic acid, the number of NADPH diaphorase neurons in the hilus and CA1 subfield was decreased, whereas the cell counts in the other hippocampal areas were to a great extent similar to those for the controls. We propose that the loss of NADPH diaphorase neurons in the hippocampus after systemic injection of kainic acid is associated with the pathophysiological processes involved in the spreading of epileptic seizure activity rather than to the direct neurotoxic effect of the kainic acid per se.
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PMID:NADPH diaphorase-containing nonpyramidal cells in the rat hippocampus exhibit differential sensitivity to kainic acid. 758 34

The regional distribution of nitric oxide synthase in the central nervous system was assessed by quantitative autoradiography using [3H]L-NG-nitro-arginine binding in wild-type mice (SV-129 and C57black/6) and in mice lacking expression of the neuronal (type 1) and endothelial (type 3) nitric oxide synthase gene. The distribution of nitric oxide synthase binding sites in wild-type mice was similar to that described for rat brain by nicotinamide adenine dinucleotide phosphate-diaphorase staining and immunohistochemistry, and as determined by quantitative autoradiography. In the wild-type mice, the densest labelling was observed in the granular layer of the olfactory bulb, tenia tecta, rhinal fissure, amygdaloid complex and molecular layer of cerebellum. The islands of Calleja, the hippocampal CA1 and CA3 subfields, dentate gyrus, cortical layers I-II, the superficial gray layer of superior colliculus and the granule layer of cerebellum displayed intermediate binding. Cortical layers III-VI, the striatum and the thalamus were only weakly labelled. Binding was saturable and of high affinity, and was displaced by 7-nitroindazole (100 microM), a potent and selective inhibitor of type 1 nitric oxide synthase, and by unlabelled L-NG-nitro-arginine (10 microM). The density of [3H]L-NG-nitro-arginine binding was dramatically reduced in all brain regions in type 1 mutant mice, whereas there were no detectable binding differences between wild-type and type 3 nitric oxide synthase mutant mice. Hence, type 1 nitric oxide synthase is the major source of [3H]L-NG-nitro-arginine binding in the mouse brain. [3H]L-NG-Nitro-arginine autoradiography may be a useful tool to quantify nitric oxide synthase in different brain areas after pharmacological or physiological manipulations.
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PMID:Brain distribution of nitric oxide synthase in neuronal or endothelial nitric oxide synthase mutant mice using [3H]L-NG-nitro-arginine autoradiography. 895 81

Co-localization of calretinin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity was studied in the rat hippocampus and dentate gyrus. Neurons co-expressing both markers (CR/NADPH-d) were observed throughout the hippocampus and dentate gyrus. However, they were more abundant in the stratum pyramidale and radiatum of CA3, stratum pyramidale of CA1, and in the juxtagranular zone of the hilus. The NADPH-d activity appeared in 37% of the calretinin immunoreactive neurons in CA3, 42% in CA1, and 36% in the dentate gyrus, whereas calretinin immunoreactivity occurred in 41% of the NADPH-d positive neurons in the hippocampus, and 16% in the dentate gyrus. The morphology and location of the double marked cells could not be used as a characteristic of the co-localizing neurons. The heavily stained NADPH-d neurons occurring mainly in CA1 do not show calretinin immunoreactivity. NADPH-d fiber swellings could be observed in close apposition to calretinin immunoreactive neurons and dendrites, suggesting synaptic contacts. It has been reported that calretinin immunoreactivity and NADPH-d activity co-localize infrequently in other areas such as the neocortex, striatum, hypothalamus and tegmental nucleus. The relatively high proportion of double marked cells found in the hippocampus and dentate gyrus could be indicative of the importance of the CR/NADPH-d interneurons in the circuitries of these areas.
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PMID:Neurons co-localizing calretinin immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the hippocampus and dentate gyrus of the rat. 903 Apr 19

The subiculum is the major output region of the hippocampal formation. We have studied pyramidal neurons in slices of rat ventral subiculum to determine if there is a correlation between nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and electrophysiological phenotype. The majority of NADPH-d-positive pyramidal neurons were found in the superficial cell layer (i.e. nearest to the hippocampal fissure) of the subiculum and appreciable NADPH-d activity was absent from pyramidal neurons in area CA1. This distribution of NADPH-d activity was mimicked by that of immunoreactivity for the neuronal isoform of nitric oxide synthase. Subicular pyramidal neurons were classified, electrophysiologically, as intrinsically burst-firing or regular spiking. After electrophysiological characterization, neurons were filled with Neurobiotin and revealed using fluorescence immunocytochemistry. The slices containing these neurons were also processed for NADPH-d. NADPH-d activity was found in six out of eight regular spiking neurons but was not found in any of 13 intrinsically burst-firing neurons (P=0.0008, Fisher's Exact Test). We conclude that in rat ventral subiculum, NADPH-d activity is present in a proportion of pyramidal neurons and indicates the presence of the neuronal isoform of nitric oxide synthase. Furthermore, amongst pyramidal neurons, NADPH-d activity is distributed preferentially to those with the regular spiking phenotype. The distribution of regular spiking neurons suggests that they may not be present to the same extent in all subicular output pathways. Thus, the actions of nitric oxide may be relatively specific to particular hippocampal connections.
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PMID:Differential expression of NADPH-diaphorase between electrophysiologically-defined classes of pyramidal neurons in rat ventral subiculum, in vitro. 925 24

Nitric oxide has been postulated as a retrograde intercellular messenger for long-term potentiation, a form of synaptic plasticity that is associated with learning and memory processes. In the present study we investigated whether the loss or survival of nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-containing neurons, which are known to synthesize nitric oxide, would be an useful indicator for evaluating the structural and functional state of the rat hippocampus after status epilepticus that is induced by intraperitoneal injection of kainic acid. Besides NADPH diaphorase histochemistry, two other histological parameters were studied: the grade of cell damage evaluated from silver-impregnated sections, and the number of somatostatin-containing neurons in different hippocampal subfields. We found that the number of NADPH diaphorase-containing neurons in the hilus and granule cell layer correlated well with spatial learning and memory performance as assessed by the Morris water-maze test. The extent of cell damage in the CA1 subfield analysed in silver-impregnated sections and the number of hilar somatostatin-containing neurons also significantly correlated with latencies in the water-maze test. Furthermore, linear regression analysis revealed that the number of somatostatin-containing neurons in the hilus explains about 50% of the variation in water-maze learning. These findings emphasize that although general structural preservation is of crucial importance for the function of the hippocampus also interneurons, such as somatostatin- and NADPH diaphorase-containing neurons, may play an important role during the acquisition phase and processing of information in hippocampal circuitry. Therefore, in addition to evaluating general cell damage, analysis of the cell loss that occurs in the interneuron subpopulations will be beneficial in verifying structural and functional deficits of the hippocampus after status epilepticus.
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PMID:Comparison of NADPH diaphorase histochemistry, somatostatin immunohistochemistry, and silver impregnation in detecting structural and functional impairment in experimental status epilepticus. 925 25

In this study, we assessed the effects of normal ageing on the number, distribution, and somal area of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-positive (NADPHd+) and tyrosine hydroxylase-immunoreactive (TH-IR) amacrine cells in human and rat retina. By using a double-labelling immunohistochemical technique, we have shown that these two enzymes are located in separate amacrine cell populations in the human retina. In normal human retinas from organ donors, we have shown that there was no change in the number, somal area, or retinal distribution of NADPHd+ neurons over an age range of 19-89 years. In contrast, there was a significant decrease (P < 0.05) of 52% in the total number of TH-IR neurons in the group aged 65-89 years compared with the group aged 19-64 years. CA1 and CA2 TH-IR neurons were reduced by 44% and 55%, respectively. In young (3 months) and old (2 years) rats, the number of NADPHd+ neurons did not decrease with ageing, but the number of TH-IR neurons was significantly reduced by 21% (P < 0.05). In a companion study on monkey retina, we have shown that a postmortem delay of 12.5 hours between death and fixation results in a decrease of 33% in the number of both NADPHd+ and TH-IR neurons in the retina compared with the number in retinas fixed immediately after death. The findings of this study on the two subsets of amacrine cells, therefore, are likely to demonstrate the consequences of ageing in the retina and might contribute to visual impairment in the elderly.
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PMID:Ageing has a differential effect on nitric oxide synthase-containing and catecholaminergic amacrine cells in the human and rat retina. 941 25

In the central nervous system (CNS), nitric oxide (NO) is thought to be involved in a variety of functions including synaptic plasticity, long term potentiation, and neurotoxicity. The aim of the present study was to investigate the expression of nitric oxide synthase (NOS) in the mouse CNS, following surgical injury to the hippocampus. NOS expression was assessed by histochemical detection of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) activity and immunohistochemistry of the inducible NOS (iNOS). Two days after injury to the CA1 hippocampal field, NADPH-diaphorase activity was detected in pyramidal and granular neurons and also in glial cells in the hippocampus, in contrast to the non-injured one where NADPH-diaphorase staining was observed only in a few interneurons. NADPH-diaphorase histochemistry combined with immunolabelling for GFAP and F4/80 demonstrated that these glial cells were astrocytes and microglia. This pattern of NOS expression is induced specifically after a hippocampal injury since lesion to the prefrontal or cerebellar cortex leads to NOS activity only in monocytes/macrophages like cells. Despite the large expression of NOS detected by NADPH-diaphorase histochemistry after lesioning the hippocampus, immunostaining for iNOS was confined to microglia. The fact that induction of high levels of NOS activity are detected in glial cells after a lesion to the hippocampus could be accounted for by the sensitivity of this structure to a high release of glutamate.
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PMID:Specific pattern of nitric oxide synthase expression in glial cells after hippocampal injury. 951 65


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