Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide synthase (NOS), an enzyme involved in synthesis of nitric oxide (NO), has been localized in many diverse cell types. In the CNS and PNS, discrete neuron cell groups express NOS constitutively. Recent evidence indicates that NOS is inducible in neurons normally not expressing NOS. After transection of peripheral nerves, NOS expression was significantly up-regulated in the axotomized sensory ganglion cells, whereas in the corresponding motor neurons NOS was not induced unless axon regeneration was prevented and ensuing neuron death became massive. Studies on axotomy-induced NOS have been limited largely to spinal nerves, with only one reported in the vagus nerve. The aim of this study was to determine whether NOS induction in motor neurons of the brainstem after axotomy is regulated in a manner similar to that of the spinal cord. By NADPH-diaphorase histochemistry and NOS immunocytochemistry, the status of NOS in neurons of the hypoglossal nucleus, dorsal motor nucleus of the vagus, and motor nucleus of the facial nerve was examined 2 weeks after unilateral transection of the respective cranial nerves, and the results were compared with those of spinal motor neurons after transection of the sciatic nerve. NOS, undetectable in neurons of the three cranial motor nuclei of sham-operated animals, was observed in about 30-50% of neurons in the cranial motor nuclei ipsilateral to axotomy, but it was not detected in spinal motor neurons after axotomy. NOS localized in axotomized cranial motor neurons was unrelated to NOS of macrophages or endothelial cells. There was no appreciable cell loss from axotomy at this period except in the dorsal motor nucleus of the vagus, where some loss was observed. The results indicate that there is a fundamental difference in the regulation of NOS expression between motor neurons of the cranial and spinal nerves. The possible role of NOS/NO acting as cytoprotective or cytotoxic agent on injured motor neurons is discussed. Motor neurons of cranial and spinal nerves may serve as a useful model to further define the roles of NOS/NO in neurons, especially after traumatic injury.
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PMID:Nitric oxide synthase in motor neurons after axotomy. 751 Mar 17

Recent studies have indicated that nitric oxide (NO)-induced cGMP synthesis is involved in different steps of neurogenesis in invertebrates. The development of putative NO synthetising elements was described earlier in the embryonic and juvenile pond snail, Lymnaea stagnalis, applying NADPH-diaphorase histochemistry (Serfozo et al., 1998). In the present study, we examined the distribution of NO synthase (NOS) during Lymnaea development by in situ hybridization for Lymnaea-NOS mRNA, histochemical, and immunohistochemical techniques for the NOS and NO-stimulated cGMP. Peripheral fibers projecting to the CNS and terminating in the ganglionic neuropils showed NOS immunoreactivity from 85% of embryonic development. At the same time, a fine dot-like, immunostaining indicated the presence of cGMP in the neuropil area. In the CNS, Lymnaea-NOS mRNA positive, as well as NOS and cGMP immunoreactive perikarya were detected first during postembryonic development; their number significantly increased from P3 juvenile stage. Some of the cell groups in the CNS containing NOS immunoreactive material also displayed Lymnaea-NOS mRNA hybridization signal and were cGMP-positive. However, in the subesophageal ganglia, the distribution of Lymnaea-NOS mRNA positive cell groups did not correspond to that of the NOS immunoreactive cells. Neurons revealing transient NOS and cGMP immunoreactivity, respectively, could also be detected in this part of the CNS. In most of the ganglia the number of Lymnaea-NOS mRNA containing and cGMP immunopositive neurons, respectively, exceeded that of the NOS immunoreactive cells from P4 juvenile stage. The localization of NADPH-diaphorase reaction also correlated well with that of the NOS immunoreactivity in the developing CNS. At the periphery, colocalization of Lymnaea-NOS mRNA signal, NOS and cGMP immunoreactivities were observed in the epithelial cells of the esophagus and mantle after hatching. The findings suggest the functional maturity of the NO/cGMP signal transduction pathway at both central and peripheral levels during the development of the snail, Lymnaea stagnalis. The differences in the localization of Lymnaea-NOS mRNA labeling and NOS immunoreactivity in the CNS and PNS can be explained by the existence of different NOS isoforms, posttranslational regulation of NOS, and/or some non-specific antibody labeling.
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PMID:Development of the nitric oxide/cGMP system in the embryonic and juvenile pond snail, Lymnaea stagnalis L. A comparative in situ hybridization, histochemical and immunohistochemical study. 1281 35

1. Nitric oxide (NO) is highly reactive gaseous molecule to which many physiological and pathological functions have been attributed in the central (CNS) and peripheral (PNS) nervous system. The present investigation was undertaken to map the distribution pattern of the enzyme responsible for the synthesis of NO, nitric oxide synthase (NOS), and especially its neuronal isoform (nNOS) in the population of primary afferent neurons of the trigeminal ganglion (TG) and mesencephalic trigeminal nucleus (MTN) of the rabbit. 2. In order to identify neuronal structures expressing nNOS we applied histochemistry to its specific histochemical marker nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd). 3. We found noticeable amount of NADPHd-exhibiting primary afferent neurons in TG of the rabbit under physiological conditions. The intensity of the histochemical reaction was highly variable reaching the maximum in the subpopulation of small-to-medium-sized neurons. The large-sized neurons were only weakly stained or actually did not posses any NADPHd-activity. In addition, NADPHd-positive nerve fibers were detected between clusters of the ganglionic cells and in the peripheral branches of the trigeminal nerve (TN). NADPHd-exhibiting MTN neurons were noticed in the whole rostrocaudal extent of the nucleus even though some differences were found concerning the ratio of NADPHd-positive versus NADPHd-negative cell bodies. Similarly, we observed striking diversity in the intensity of NADPHd histochemical reaction in the subpopulations of small-, medium-, and large-sized MTN neurons. 4. The predominant localization of NADPHd in the subpopulation of small-to-medium-sized TG neurons which are generally considered to be nociceptive suggests that NO probably takes part in the modulation of nociceptive inputs from the head and face. Furthermore, we tentatively assume that NADPHd-exhibiting MTN neurons probably participate in transmission and modulation of the proprioceptive impulses from muscle spindles of the masticatory muscles and mechanoreceptors of the periodontal ligaments and thus provide sensory feedback of the masticatory reflex arc.
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PMID:Distribution of NADPH diaphorase-exhibiting primary afferent neurons in the trigeminal ganglion and mesencephalic trigeminal nucleus of the rabbit. 1677 44

Nitric oxide (NO) signaling results in both neurotoxic and neuroprotective effects in CNS and PNS neurons, respectively, after nerve lesioning. We investigated the role of NO signaling on optic nerve regeneration in the goldfish (Carassius auratus). NADPH diaphorase staining revealed that nitric oxide synthase (NOS) activity was up-regulated primarily in the retinal ganglion cells (RGCs) 5-40 days after axotomy. Levels of neuronal NOS (nNOS) mRNA and protein also increased in the RGCs alone during this period. This period (5-40 days) overlapped with the process of axonal elongation during regeneration of the goldfish optic nerve. Therefore, we evaluated the effect of NO signaling molecules upon neurite outgrowth from adult goldfish axotomized RGCs in culture. NO donors and dibutyryl cGMP increased neurite outgrowth dose-dependently. In contrast, a nNOS inhibitor and small interfering RNA, specific for the nNOS gene, suppressed neurite outgrowth from the injured RGCs. Intra-ocular dibutyryl cGMP promoted the axonal regeneration from injured RGCs in vivo. None of these molecules had an effect on cell death/survival in this culture system. This is the first report showing that NO-cGMP signaling pathway through nNOS activation is involved in neuroregeneration in fish CNS neurons after nerve lesioning.
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PMID:Nitric oxide-cGMP signaling regulates axonal elongation during optic nerve regeneration in the goldfish in vitro and in vivo. 1945 64