Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clusterin (SGP-2) is a newly described glycoprotein associated with several putative functions including responses to brain injury. This study reports the regional and cell type expression of clusterin mRNA and its encoded glycoprotein in the rat brain; a limited comparison was also done with the human brain. Using in situ hybridization combined with immunocytochemistry, we found that astrocytes and neurons may express clusterin mRNA in the normal adult brain. While astrocytes throughout the brain contained clusterin mRNA, there was regional selectivity for neuronal clusterin expression. In the striatum, clusterin mRNA was not detected in neurons. Only a subset of substantia nigra dopaminergic neurons or locus ceruleus noradrenergic neurons (tyrosine hydroxylase immunopositive) contained clusterin mRNA. However, neuronal clusterin mRNA was prevalent in pontine nuclei and in the red nucleus of the midbrain tegmentum. Similarly, clusterin mRNA was prevalent in both rat and human hippocampal neuron-specific enolase immunopositive pyramidal neurons, although rat CA1 neurons had less mRNA than CA2-CA3 neurons. Monotypic primary cell cultures from the neonatal rat showed clusterin mRNA in both neurons and astrocytes, but not in microglia. By immunocytochemistry, no clusterin immunopositive glia were observed in any region of the rat brain, confirming previous studies. However, clusterin immunopositive cells (putative neurons) were observed in the Purkinje cell layer of the cerebellum, medial and interposed cerebellar nuclei, trigeminal motor nucleus, and red nucleus. Finally, in vitro studies suggest that astrocytes, but not neurons, secrete clusterin, which is pertinent to clusterin immunodeposits found after experimental lesioning.
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PMID:Clusterin (SGP-2): a multifunctional glycoprotein with regional expression in astrocytes and neurons of the adult rat brain. 813 68

Equine grass sickness (EGS) is a primary dysautonomia characterised pathologically by lesions in autonomic ganglia, enteric plexi and specific nuclei in the CNS. Immunocytochemistry and lectin histochemistry of the autonomic ganglia were used to determine whether abnormalities can be detected in specific proteins or cellular organelles. EGS ganglia contained a mixture of morphologically normal and abnormal neurons, the former appearing identical to cells from control animals. Affected cells showed marked disturbances in neurofilament (NF) proteins and beta-tubulin, major components of the cytoskeleton; in most neurons immunoreactivity was reduced or absent while the distribution was altered in the remainder. Staining for neuron-specific enolase, a pan-neuronal marker, was severely reduced or absent, as was reactivity for the catecholaminergic enzyme tyrosine hydroxylase. However, affected neurons showed a marked increase in dopamine-beta-hydroxylase (D beta H), another enzyme associated with noradrenaline synthesis. Wheat germ agglutinin and Griffonia simplicifolia B4 lectin histochemistry was used to label membranes of the Golgi apparatus, which stained as discrete curvilinear perinuclear profiles. All affected neurons showed abnormalities with either complete loss of reaction or amorphous centrally located lectin staining. The results indicate perturbation in a wide variety of cytoplasmic and cytoskeletal proteins. In the majority of instances there is a decrease in stainable protein; the increase in D beta H may indicate a failure to be transported down the axon with resultant accumulation in the perikaryon. Loss of a recognisable Golgi structure appears to be an early event in the neuropathology of EGS.
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PMID:Immunocytochemical and lectin histochemical study of neuronal lesions in autonomic ganglia of horses with grass sickness. 822 78

The autoxidation of L-DOPA or dopamine (DA) and the metabolism of DA by monoamine oxidase generate a spectrum of toxic species, namely, hydrogen peroxide, oxy radicals, semiquinones, and quinones. When primary dissociated cultures of rat mesencephalon were incubated with L-DOPA (200 microM) for 48 h, the number of tyrosine hydroxylase-positive neurons (DA neurons) was reduced to 69.7% of control values, accompanied by a decrease in [3H]DA uptake to 42.3% of control values; the remaining DA neurons exhibited reduced neurite length and overall deterioration. Lack of simultaneous change in the number of neurons stained with neuron-specific enolase indicated that toxicity was relatively specific for DA neurons. At the same time, the level of GSH, a major cellular antioxidant, rose to 125.2% of control values. Thus, exposure of mesencephalic cultures to L-DOPA results in both damaging and antioxidant actions. Ascorbate (200 microM), an antioxidant, prevented the rise in GSH. The effect of ascorbate on GSH points to an oxidative signal to initiate the rise in GSH content. On the other hand, neither inhibition of monoamine oxidase with pargyline nor addition of superoxide dismutase or catalase to the culture medium prevented the rise in GSH level or the loss in [3H]DA uptake. The latter results tend to exclude the products of monoamine oxidase activity or the presence of hydrogen peroxide or superoxide in the medium as responsible agents for the rise in GSH or neuronal toxicity. In cultures treated with L-buthionine sulfoximine (L-BSO), an inhibitor of GSH synthesis, L-DOPA prevented cell death by L-BSO.
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PMID:Toxic and protective effects of L-dopa on mesencephalic cell cultures. 837 99

A number of marker substances for neuronal and neuroendocrine cells have been demonstrated in the cytoplasm of the interstitial Leydig cells of human testes using basic immunocytochemical methods and some of their modifications. We were able to reveal immunoreactivity for enzymes involved in the synthesis of the catecholamines dopamine and noradrenaline (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine-beta-hydroxylase), for the indolamine 5-hydroxytryptamine (serotonin), as well as for a number of well-known neuronal markers such as the neurofilament protein 200, synaptophysin, chromogranin A + B, the neural cell-adhesion molecule (N-CAM), the microtubule-associated protein (MAP-2), and the calcium-binding proteins: S-100, calbindin and parvalbumin. Immunoreactivity for these substances was found in the majority of the interstitial cells although differences in the staining intensity among the individual Leydig cells and among Leydig cells from different patients were observed. At the electron-microscopic level the Leydig cell cytoplasm was seen to contain microtubules, intermediate- and microfilaments as well as clear (40-60 nm) and dense-core (100-300 nm) vesicles, providing a morphological correlate for some of the immunocytochemical results. Although individual marker substances are not absolutely specific for nerve and neuroendocrine cells, the results obtained, together with the already established neuron-specific enolase-, substance P-, methionine-enkephalin- and proopiomelanocortin (POMC)-derived peptide-like immunoreactivity, provide strong evidence for the neuroendocrine (paraneuronal, APUD-like) nature of the Leydig cells of the human testis.
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PMID:The Leydig cell of the human testis--a new member of the diffuse neuroendocrine system. 847 1

The neural control of human nasal vasculature is still not completely understood. This study was performed to demonstrate the innervation pattern of the different vessel types and to distinguish between nor-adrenergic and cholinergic structures. General innervation was demonstrated using antibodies to neuron-specific enolase and S-100 protein. Autonomic structures were shown by using antibodies to tyrosine hydroxylase and choline acetyltransferase (ChAT). In addition, choline acetyltransferase (AChe) histochemistry was performed. Nasal vasculature is controlled by a dense innervation that increases with the thickness of the tunica media. While all larger vessels show a mixed autonomic innervation, sympathetic structures seem to predominate in veins. These findings demonstrate that classic neurotransmitters play a major role in the regulation of nasal vasculature. The stronger innervation of arteries and cushion veins underlines their central position in the control of nasal air flow.
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PMID:Basic innervation pattern and distribution of classic autonomic neurotransmitters in human nasal mucosal vasculature. 861 90

This study examines the effects of high K+ concentration on the growth and development of mesencephalic cells and their glutamate vulnerability. Mesencephalic cell cultures obtained from Wistar rat embryos on the 14th gestational day were maintained for 14 days in medium with either normal (4.2 mM) or elevated (24.2 mM) potassium concentration. There was no significant difference due to various K+ concentration in cell growth and survival up to day in vitro (DIV) 13-14. In order to test the glutamate (Glu) vulnerability, cultures were treated with 100 mu M Glu for 15 min in salt solution on the DIV 3,6,8 and 13. Glu-induced neuronal damage was estimated 24 h later by measuring the neuron-specific enolase (NSE) content in the culture medium and by counting the number of tyrosine hydroxylase-immunoreactive (TH-IR) neurons. Glu had no damaging effect on the cells on DIV 3, but became pronounced beyond DIV 6. Elevated potassium concentration 24.2 mM) in the culture medium during development significantly increased neuronal vulnerability to Glu treatment, indicated by a higher increase of NSE content in the medium and by a more pronounced Glu-induced decrease of the number of TH-IR cells. The Glu-induced decrease of the number of TH-IR cells and of NSE-IR cells let us conclude that dopaminergic neurons are more vulnerable to glutamate than other neurons from mesencephalic culture.
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PMID:Elevated potassium enhances glutamate vulnerability of dopaminergic neurons developing in mesencephalic cell cultures. 863 40

Grafted islets become denervated due to the islet transplantation procedure. The aim of the present study was 1) to examine whether islet grafts in the liver, the spleen, and under the kidney capsule in rats become reinnervated following the transplantation and experimental procedures used in our laboratory, 2) whether there is any difference in reinnervation at these different sites, and 3) how these results relate to previous physiological experiments. Isogeneic isolated islets were transplanted into diabetic Albino Oxford rats, resulting in normoglycaemia. After at least 5 wk, graft-receiving organs were removed and several antibodies were employed to detect insulin, neuron-specific proteins, and cholinergic and noradrenergic nerve fibers. Islets in all three receiving organs contained viable insulin-positive B-cells. Neuron-specific enolase (NSE) as well as the growth-associated protein B-50 was observed at all sites. The cholinergic marker choline acetyltransferase (ChAT) was localized in islets grafts at all sites, but with the lowest density in the spleen. Staining for the noradrenergic markers tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) was observed in islet grafts at all sites with the lowest density in grafts under the kidney capsule. All these neurochemical substances were most frequently observed in fibers associated with blood vessels, which may be the route along which nerves grow into the graft. It can be concluded that 1) islet grafts in the liver, in the spleen and under the kidney capsule become reinnervated; 2) the innervation pattern of the islet grafts differs only slightly from that in the control pancreatic islets; and 3) in combination with our previously physiological data, we can conclude that these nerve fibers are, at least partly, functionally active.
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PMID:Noradrenergic and cholinergic reinnervation of islet grafts in diabetic rats. 866 73

The immunocytochemical characterization of cell lines originating from thyroid medullary carcinoma, i.e. human TT cells and rat rMTC 6-23 cells, was undertaken. The immunocytochemical studies were supplemented by ultrastructural studies, including ultrastructural immunocytochemistry, and by radioimmunological estimation of calcitonin secretion to the medium. In rMTC 6-23 cells (subcultures 24 to 30), no hormone presence was demonstrated immunocytochemically, which corresponded to the absence of secretory granules at the ultrastructural level. Of various proteins sought, only neuron-specific enolase could be demonstrated. Nevertheless, the cells secreted calcitonin into the medium. TT cells (passages 145 to 160) produced secretory granules. The granules contained calcitonin, calcitonin gene-related peptide, somatostatin, neurotensin, met-enkephalin, leu-enkephalin, gastrin releasing peptide, parathyroid hormone-related protein, functional proteins of the chromogranin group and synaptophysin. Other functional proteins found in the cytosol of TT cells included non-specific enolase, calbindin and tyrosine hydroxylase. Receptor for calcitriol was localized in the cell nucleus. Marker proteins were localized in the cytosol (carcinoembryonic antigen) and in the cell skeleton (alpha-tubulin, cytokeratin). Following changes in ionized calcium levels in the medium, changes in calcitonin secretion and in immunocytochemical detectability of some hormones and functional proteins were observed. TT cells demonstrated the expression of numerous hormones and functional proteins associated with calcitonin secretion. Further, the cells in their ultrastructure, immunocytochemical and secretory characteristics, resemble more closely normal parafollicular cells of the thyroid and, in our opinion, represent a more appropriate model for functional studies.
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PMID:Immunocytochemical characterization of two thyroid medullary carcinoma cell lines in vitro. 878 64

The neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), are established survival promoting molecules for dopaminergic (DAergic) neurons cultured from the fetal rat midbrain floor. We have cultured and compared the survival of embryonic day (E) 14 mesencephalic cells in fully defined, serum-free medium, with serum-primed cultures (one hour during dissociation). Cultures were characterized using antibodies against neuron-specific enolase (NSE), tyrosine hydroxylase (TH), vimentin, glial fibrillary acidic protein (GFAP), and the antigen A2B5. The absolute absence of serum did not reduce the survival of TH-positive DAergic neurons nor alter the percentages of cells staining for the above markers. Transforming growth factor-beta 3 (TGF-beta 3) and glial cell line-derived neurotrophic factor (GDNF), two members of the TGF-beta superfamily, both promoted the survival of TH-positive cells (TGF-beta 3: 2-fold; GDNF: 1.6-fold) over the 8-day culture period. Survival mediated by TGF-beta 3 and GDNF was independent of whether or not the cells had been initially exposed to serum. In contrast, the survival promoting effects of BDNF and NT-4 were crucially dependent on serum priming. RT-PCR for the full-length trkB high affinity neurotrophin receptor revealed its presence in both culture systems. We conclude that priming with serum is important to make DAergic neurons fully responsive to BDNF and NT-4. Underlying mechanisms might be sought at the level or distal of trkB receptor expression, without excluding the possiblity that serum elicits production of growth factors that synergistically act with neurotrophins in these cultures.
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PMID:The survival response of mesencephalic dopaminergic neurons to the neurotrophins BDNF and NT-4 requires priming with serum: comparison with members of the TGF-beta superfamily and characterization of the serum-free culture system. 884 70

The innervation in human taste buds of the foliate and circumvallate papillae was studied immunohistochemically using several neuronal markers in patients with Alzheimer's disease (AD) and their control (ADC) patients. Antisera to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), tyrosine hydroxylase (TH), dopamine-beta hydroxylase (DbetaH) and calcitonin gene-related peptide (CGRP) were used in immunofluorescence and streptavidin-biotin-peroxidase complex studies. The antiserum to PGP 9.5 stained a greater number of intragemmal nerve fibers in taste buds than that of other antisera. PGP 9.5 immunoreactivity was strictly localized in the nerve fibers, whereas NSE immunoreactivity was observed not only in the nerve fibers, but also in taste bud cells. Intragemmal TH- and DbetaH-immunoreactive nerve fibers were not identified in taste buds. Only a few intragemmal nerve fibers immunoreactive for anti-CGRP antiserum were observe in a small number of taste buds. Furthermore, quantitive analysis in AD and ADC patients demonstrated that the mean number of PGP 9.5-immunoreactive intragemmal nerve fibers in taste buds of the foliate and circumvallate papillae decreased significantly in AD patients. These results indicated that PGP 9.5 is a most suitable molecular marker for the demonstration of the extrinsic innervation in human taste buds, and that the decreased innervation may account partially for the decrement in chemosensory capacity in AD patients.
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PMID:Innervation in human taste buds and its decrease in Alzheimer's disease patients. 892 42


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