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)

We report the presence in rat spinal cord of a novel neuronal system expressing tyrosine kinase receptor (trkA), the high affinity receptor for nerve growth factor (NGF). TrkA immunoreactive cell bodies were observed in the intermediate grey matter of the spinal cord and were classified into three main groups: central canal cells located dorsolateral to the aqueduct, partition cells located between lamina X, and the lateral border of the intermediate grey, and a morphologically heterogeneous group which included large cells located near the lateral border. In situ hybridization confirmed that cells in all these areas express trkA mRNA. Combined immunofluorescence and retrograde Fluoro-Gold labelling was used to further characterise the projections and neurotransmitter profile of the trkA cells. Although often located in the vicinity of preganglionic cell groups, trkA immunoreactive cells are not themselves preganglionic. Rather, the central canal and partition cells belong to a neurochemically complex cholinergic propriospinal system. Many partition cells coexpress trkA, choline acetyltransferase (ChAT), the low affinity neurotrophin receptor, p75, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d). In contrast, trkA immunoreactive central canal cells express ChAT, but do not express p75 and only a subpopulation express NADPH-d. The large trkA immunoreactive cells located on the lateral border do not express ChAT. TrkA immunoreactive fibres were also present and were located in the dorsal horn, in the dorsal columns, and in a bundle ventral to the aqueduct. However, double labelling revealed that the trkA immunoreactive fibres are not intrinsic but are primary afferent in origin and coexpress p75. The location of this novel trkA neuronal system is consistent with it having a role in the segmental integration of autonomic outflow. NGF could affect this system by modulating neuronal phenotype and/or synaptic efficacy.
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PMID:TrkA immunoreactive neurones in the rat spinal cord. 930 Jul 70

Cholinergic basal forebrain neurons appear to play a key role in cognition and attention. In rat, basal forebrain neurons express multiple proteins including the high-affinity signal transducing tyrosine kinase A receptor for nerve growth factor, the neuropeptide galanin and nitric oxide synthase, a marker for the novel neurotransmitter nitric oxide. The present study was undertaken to define the relationship between neurons expressing each of these markers within the medial septum-vertical limb of the diagonal band, horizontal limb of the diagonal band and nucleus basalis in colchicine pre-treated rats. Tyrosine kinase A-immunopositive neurons were seen throughout all subfields of the basal forebrain. In contrast, nitric oxide synthase- and galanin-immunoreactive neurons were mainly distributed within the septal-diagonal band complex. Co-localization experiments revealed that virtually all nitric oxide synthase-positive neurons (visualized by nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry) also contained tyrosine kinase A, whereas many fewer tyrosine kinase A neurons were nicotinamide adenine dinucleotide phosphate-diaphorase positive within the medial septum-vertical limb of the diagonal band. Within the horizontal limb of the diagonal band, numerous nicotinamide adenine dinucleotide phosphate-diaphorase neurons expressed tyrosine kinase A, whereas only a small number of tyrosine kinase A neurons contained nicotinamide adenine dinucleotide phosphate-diaphorase. Within the nucleus basalis very few neurons were nicotinamide adenine dinucleotide phosphate-diaphorase reactive, and a minor number contained tyrosine kinase A. Additional co-localization experiments revealed minor percentages of neurons containing nicotinamide adenine dinucleotide phosphate-diaphorase and galanin immunoreactivity within the various subfields of the basal forebrain. Within the horizontal limb of the diagonal band minor numbers of nicotinamide adenine dinucleotide phosphate-diaphorase-reactive perikarya displayed galanin. Similarly, only a few galanin-containing neurons expressed nicotinamide adenine dinucleotide phosphate-diaphorase. The existence of tyrosine kinase A, nitric oxide synthase and galanin within select neuronal subgroups of the cholinergic basal forebrain suggests that these perikarya are responsive to a complex set of chemical signals. A greater understanding of the chemical signature of the cholinergic basal forebrain neurons will provide the insight required to develop novel pharmacological approaches aimed at preventing or slowing the degenerative processes that effect these neurons in aging and pathologic disorders.
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PMID:Tyrosine kinase A, galanin and nitric oxide synthase within basal forebrain neurons in the rat. 974 Apr 4

Nitric oxide synthase (NOS) containing nerve regeneration can be seen six months after unilateral cavernous nerve neurotomy in rats. However, its molecular mechanism is still unknown. It is believed that growth factors are involved in this phenomenon. In this study we investigated the change of NOS containing nerve fibers and the RNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha, TGF-beta 1, TGF-beta 2. TGF-beta 3 and NOS on the penis after cavernous nerve neurotomy in rats. Male rats were divided into three groups: (1) sham operation (N = 10); (2) unilateral neurotomy of a 5 mm segment of the cavernous nerve (N = 15); and (3) bilateral neurotomy (n = 15). Electrostimulation of the intact cavernous nerve or pelvic ganglion was performed at one, three and six months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was used to identify NOS in the penile nerve fibers. The gene expression for growth factors and bNOS was investigated in corporal tissue by reverse transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. One month after neurotomy, both unilateral and bilateral neurotomy groups showed a significant decrease in NOS-containing nerve fibers on the dorsal and intracavernosal nerves on the side of neurotomy, and a significantly lower mRNA expression of bNOS, IGF-I and TGF-beta 2. At three months, the number of NOS-containing nerve fibers in the unilateral neurotomy group increased only slightly but at six months those in the intracavernosal nerve increased in a significant amount (P < 0.0001), however mRNA expression of bNOS, IGF-I and TGF-beta 2 showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dorsal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvic ganglion stimulation. In the unilateral neurotomy group at six months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regeneration derives from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater maximal intracavernosal pressure and a shorter latency period at six months than at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta 2 may play a key role in regeneration of NOS-containing nerve fibers in the dorsal and intracavernosal nerves after unilateral cavernous nerve injury.
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PMID:The role of growth factor on regeneration of nitric oxide synthase (NOS)--containing nerves after cavernous neurotomy in the rats. 1046 23

The molecular mechanism of nitric oxide synthase (NOS)-containing nerve regeneration is still unknown. It is believed that growth factors are involved in this phenomenon. We investigated the change of NOS containing nerve fibers and the mRNA expression of insulin like growth factor (IGF)-I, nerve growth factor (NGF), transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, TGF-beta3, vascular endothelial growth factor (VEGF), endothelial NOS (eNOS) and neuronal NOS (nNOS) on the penis after cavernous nerve neurotomy in rats. Male rats were divided into four groups: (1) sham operation (n = 14); (2) unilateral neurotomy of a 5 mm segment of the cavernous nerve (n = 21); (3) unilateral neurotomy with growth hormone (n = 14); and (4) bilateral neurotomy (n = 21). Electrostimulation of the intact cavernous nerve or pelvic ganglion were performed at one, three and six months. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and immunohistochemistry were used to identify NOS in the penis. The gene expression for growth factors, eNOS and nNOS were investigated in corporal tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). One month after neurotomy, both unilateral and bilateral neurotomy groups showed significant decreases in NOS-containing nerve fibers on the dorsal and intracavernosal nerves on the side of neurotomy. Significantly lower mRNA expression of nNOS, IGF-I and TGF-beta2, higher mRNA expression of eNOS and VEGF189 were shown in these groups. At three months, the number of NOS-containing nerve fibers in the unilateral neurotomy group increased only slightly, while the GH-treated group showed a significant increase. At six months, those in the intracavernosal nerve only increased in a significant amount (P < 0.0001), however mRNA expression of nNOS, IGF-I and TGF-beta2 showed a significant increase as early as at three months. After bilateral neurotomy, the NOS-positive nerve fibers in the dorsal and intracavernosal nerve were significantly decreased at one month and remained so at six months; no erectile response could be elicited by pelvic ganglion stimulation. In the unilateral neurotomy group at six months, more NOS-positive neurons in the pelvic ganglia were found on the intact side than on the side of the neurotomy (P < 0.003), indicating that the regeneration derived from pelvic ganglion neurons on the intact side. Furthermore, electrostimulation in the unilateral neurotomy group revealed a greater maximal intracavernosal pressure and a shorter latency period at six months than at one month (P < 0.014, P < 0.001, respectively). These data suggest that IGF-I and TGF-beta2 may play a key role in the regeneration of nNOS-containing nerve fibers in the dorsal and intracavernosal nerves, and eNOS increases temporarily in the intracavernous involving VEGF189 after unilateral cavernous nerve injury.
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PMID:IGF-I and TGF-beta2 have a key role on regeneration of nitric oxide synthase (NOS)-containing nerves after cavernous neurotomy in rats. 1055 3

We have examined nerve growth factor (NGF)-triggered signaling in two NIH3T3 cell lines exogenously expressing the NGF receptor, TrkA. TRK1 cells cease to proliferate and extend long processes in response to NGF, while E25 cells continue to proliferate in the presence of NGF. These two cell lines express similar levels of TrkA and respond to NGF with rapid elevation of mitogen-activated protein kinase (MAPK) activity. MAPK activation is slightly more sustained for E25 cells than for TRK1 cells, although sustained activation of MAPK has been suggested to cause cell-cycle arrest. As judged by NADPH-diaphorase staining, nitric oxide synthase (NOS) activity is increased in TRK1 cells upon exposure to NGF. In contrast, diaphorase staining in E25 cells is unaffected by NGF treatment. Immunocytochemistry shows that levels of the brain NOS (bNOS) isoform are increased in TRK1, but not E25, cells exposed to NGF. Furthermore, Western blots show that NGF elevated cyclin-dependent kinase inhibitor, p21(WAF1), in TRK1 cells only. NGF-induced p21(WAF1) expression, cell-cycle arrest and process extension are abolished by N-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NOS. The inactive enantiomer, D-NAME, did not inhibit these responses. Furthermore, even though E25 cells do not respond to NGF or nitric oxide donors, they do undergo a morphological change in response to NGF plus a nitric oxide donor. Therefore, NOS and p21(WAF1) are induced only in the TrkA-expressing NIH3T3 cell line that undergoes cell-cycle arrest and morphological changes in response to NGF. These results demonstrate that sustained activation of MAPK is not the sole determining factor for NGF-induced cell-cycle arrest and implicate NO in the cascade of events leading to NGF-induced morphological changes and cell-cycle arrest.
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PMID:Cell-cycle arrest in TrkA-expressing NIH3T3 cells involves nitric oxide synthase. 1118 Apr 9