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

Secretoneurin is a novel 33-amino-acid neuropeptide produced by endoproteolytic processing from secretogranin II, which is a member of the chromogranin/secretogranin family. In this immunocytochemical study, we compared the distribution pattern of secretoneurin immunoreactivity with that of tyrosine hydroxylase, calbindin, substance P, and Leu-enkephalin in adjacent sections of rat forebrain. Secretoneurin appeared mainly in varicosities and fibers. Only a few cell bodies were stained. In the nucleus accumbens, a partial overlap of secretoneurin-immunoreactive patches with enkephalin-immunopositive areas was found. Secretoneurin displayed low to moderate levels of immunoreaction in calbindin-rich as well as in calbindin-immunonegative areas of the caudate-putamen. In the globus pallidus, entopeduncular nucleus, and substantia nigra, secretoneurin immunoreactivity was oriented ventromedially preferentially in woolly fibers. The dense immunostaining in the medial nucleus accumbens was directly continuous with dense secretoneurin immunoreactivity in the bed nucleus of the stria terminalis. Two strongly secretoneurin-immunopositive bands, one in the sublenticular portion and a smaller one along the posterior limb of the anterior commissure, interconnected the highly secretoneurin-immunopositive centromedial amygdala with the bed nucleus of the stria terminalis. Thus, the distribution pattern of secretoneurin immunoreactivity provides a marker of the extended amygdala that forms a continuum between the centromedial amygdala and the bed nucleus of the stria terminalis.
 ...
PMID:Evidence for a high density of secretoneurin-like immunoreactivity in the extended amygdala of the rat. 774 36

Double-labelling immunofluorescence was applied on single sections of the rat superior cervical ganglion to evaluate neurochemistry and connectivity of intraganglionic SIF cells. The synaptic vesicle membrane protein synaptophysin and secretoneurin, a newly discovered neuropeptide derived from secretogranin II, proved reliable molecular markers of this cell type, whereas serotonin and tyrosine hydroxylase immunoreactivities were observed in slightly incongruent SIF cell subpopulations. Immunolabelling for vasoactive intestinal polypeptide and neuropeptide Y occurred in few SIF cells. None of the above immunoreactivities were visibly altered by preganglionic or postganglionic denervation, while some SIF cells were immunolabelled for galanin or for the neuronal microtubule-associated protein MAP2 after postganglionic denervation. SIF cells were nonreactive for the pan-neuronal marker protein gene product (PGP) 9.5 or neurofilament 160 kD. Intense staining of NADPH-diaphorase in some SIF cells, suggesting catalytic activity of nitric oxide synthase, could not be substantiated by immunoreactivity for this enzyme. SIF cells were approached by nonidentical fiber populations immunoreactive for PGP 9.5, neurofilament, or neuropeptide Y, whereas immunoreactivities for galanin and vasoactive intestinal polypeptide were colocalized in fiber meshes around SIF cells. The findings indicate (1) neurochemical SIF cell heterogeneity, (2) SIF cell plasticity in response to ganglionic perturbation, and (3) a differentiated innervation of SIF cells in the rat superior cervical ganglion.
 ...
PMID:Immunohistochemistry of small intensely fluorescent (SIF) cells and of SIF cell-associated nerve fibers in the rat superior cervical ganglion. 781 35

Bovine chromaffin cell cultures were treated with either reserpine or alpha-methyl-p-tyrosine for up to 10 days. Afterwards the cells were harvested and the degree of proteolytic processing of secretogranin II, chromogranin A and chromogranin B was determined by immunoblotting and HPLC followed by RIA. There was a significant increase in the proteolysis of all three chromogranins after 4-6 days in the presence of reserpine. The small peptides formed in the presence of reserpine in vitro are also produced in vivo. A similar effect was observed with alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, but the response took up to 10 days to develop. Both drugs decreased catecholamine levels but reserpine was more effective, reaching a high degree of depletion after 4 days. In addition, experiments in vitro indicate that low millimolar amounts of either adrenaline (IC50 5.2 mM) or noradrenaline (IC50 2.4 mM) can significantly impair the proteolytic activity of recombinant murine prohormone convertase 1 when assayed with synthetic fluorogenic and/or peptidyl substrates. We conclude that a lowering of catecholamine levels in chromaffin granules leads to a concomitant increase in proteolytic processing of all secretory peptides. Apparently within chromaffin granules the endoproteases are inhibited by catecholamines and thus their removal leads to increased proteolysis.
 ...
PMID:Processing of chromogranins in chromaffin cell culture: effects of reserpine and alpha-methyl-p-tyrosine. 867 Jan 75

TrkA high-affinity receptors are essential for the normal development of sympathetic paravertebral neurons and subpopulations of sensory neurons. Paravertebral sympathetic neurons and chromaffin cells of the adrenal medulla share an ontogenetic origin, responsiveness to NGF, and expression of TrkA. Which aspects of development of the adrenal medulla might be regulated via TrkA are unknown. In the present study we demonstrate that mice deficient for TrkA, but not the neurotrophin receptor TrkB, show an early postnatal progressive reduction of acetylcholinesterase (AChE) enzymatic activity in the adrenal medulla and in preganglionic sympathetic neurons within the thoracic spinal cord, which are also significantly reduced in number. Quantitative determinations of specific AChE activity revealed a massive decrease (-62%) in the adrenal gland and a lesser, but still pronounced, reduction in the thoracic spinal cord (-40%). Other markers of the adrenal medulla and its innervation, including various neuropeptides, chromogranin B, secretogranin II, amine transporters, the catecholamine-synthesizing enzymes tyrosine hydroxylase and PNMT, synaptophysin, and L1, essentially were unchanged. Interestingly, AChE immunoreactivity appeared unaltered, too. Preganglionic sympathetic neurons, in contrast to adrenal medullary cells, do not express TrkA. They must, therefore, be affected indirectly by the TrkA knock-out, possibly via a retrograde signal from chromaffin cells. Our results suggest that signaling via TrkA, but not TrkB, may be involved in the postnatal regulation of AChE activity in the adrenal medulla and its preganglionic nerves.
 ...
PMID:Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice. 899 44

The family of chromogranins/secretogranin peptides comprises three major subtypes: chromogranin A, chromogranin B and secretogranin II. We have characterized these proteins in rat vas deferens and pelvic ganglia by using two approaches. Firstly, extracts of rat vas deferens were subjected to molecular sieve chromatography followed by radioimmunoassay. The results indicate that, in the peripheral nerves of this organ, chromogranin B and secretogranin II are processed to small peptides, i.e. PE-11 and secretoneuron, respectively. Secondly, we investigated the localization of each of these peptides in the rat pelvic ganglia and vas deferens. Comparisons with the distribution of tyrosine hydroxylase, choline acetyltransferase, vesicular acetylcholine transporter and SV2 were carried out in double labelling studies. All tyrosine hydroxylase-positive neurons contained neuropeptide Y, but many neuropeptide Y-containing neurons were negative for tyrosine hydroxylase. In the pelvic ganglia, chromogranin A was widely localized in the neuropeptide-positive neurons and 65% of chromogranin A-containing neurons were positive for tyrosine hydroxylase, suggesting their adrenergic nature. However, in nerve terminals of the vas deferens, chromogranin A was present at very low, or undetectable, levels. The chromogranin B-derived peptide PE-11, on the other hand, was absent from the large-sized, tyrosine hydroxylase-positive neurons, but present in some small-sized neurons that were choline acetyltransferase/vesicular acetylcholine transporter-positive and tyrosine hydroxylase-negative. In the vas deferens, PE-11 was present with intense immunoreactivity in nerve terminals of the lamina propria beneath the epithelium, but it was very sparse in the muscular layer and co-localized with vesicular acetylcholine transporter-like immunoreactivity, suggesting a cholinergic nature. The secretogranin II-derived peptide secretoneurin was distributed with strong immunoreactivity in the somata of pelvic ganglion neurons, 72% of which also contained tyrosine hydroxylase, as well as in nerve terminals in the muscular layer and the lamina propria of the vas deferens. Most, if not all, secretoneurin-positive terminals in the pelvic ganglia and the vas deferens were positive for choline acetyltransferase/vesicular acetylcholine transporter-like immunoreactivity. Retrograde tracing with FluoroGold demonstrated that the majority of FluoroGold-labelled neurons in the pelvic ganglia were positive for either chromogranin A or secretoneurin. The present study indicates that chromogranins A and B and secretogranin II are proteolytically processed to a high degree in the nerves of the rat vas deferens. Furthermore, they are heterogeneously localized in subsets of neurons of the pelvic ganglia and in different sets of nerve terminals in the vas deferens, suggesting that each of these peptides may play distinct roles in neurons of the autonomic nervous system to the vas deferens.
 ...
PMID:Distribution of chromogranins A and B and secretogranin II (secretoneurin) in rat pelvic neurons and vas deferens. 952 81

The chromogranin family comprises chromogranin A and B, and secretogranin II. The present study has focused on the axonal transport of chromogranins/secretogranin II and their detailed distribution in peripheral nerves and the spinal cord. With radioimmunoassay (RIA) and column chromatography, we first studied the processing of chromogranin B and secretogranin II during axonal transport. No larger precursors of these peptides were detected in the sciatic nerves, indicating that they are already processed to a high degree early during axonal transport. We also analysed nerve segments above and below a crush, using RIA, in order to compare these accumulation data with those obtained by the cytofluorimetric-scanning (CFS) technique. For the latter technique, the amounts of accumulation distal to the crush (presumably representing recycling and retrogradely transported peptides) were 30-40% of the amounts in the proximal accumulation for chromogranin A and secretoneurin, in contrast to chromogranin B, which showed 15% recycling. With the RIA, the corresponding values for secretoneurin and PE-11 (antibody against chromogranin B) were 42% and 14%, respectively. Therefore, the data obtained by CFS were in excellent agreement with those obtained by RIA. In crushed sciatic nerves, chromogranin A was present in large axons as well as in small- and medium-sized axons. Chromogranin B was mainly restricted to large axons, while secretoneurin was localized to bundles of small axons. This differential distribution was also found in the spinal roots and in the peripheral terminals. Chromogranin A was present in both ventral and dorsal roots, and chromogranin B was detected in ventral roots and in large sensory axons in the dorsal roots. Secretoneurin was dominant in the dorsal root. Double-labelling studies with antibodies against choline acetyltransferase/vesicular acetylcholine transporter, or against tyrosine hydroxylase, confirmed that chromogranin A was distributed in cholinergic, sensory, as well as adrenergic neurons. Chromogranin B was mainly present in cholinergic motor neurons and large sensory neurons, and secretoneurin was restricted to adrenergic and sensory neurons. The present study demonstrates that chromogranins A and B, and secretoneurin are transported with fast axonal transport in the peripheral nerves, with different amounts of recycling, and that they are differentially distributed in different types of neurons in the peripheral nervous system and the spinal cord, suggesting that each of them may play a special role in subsets of neurons.
 ...
PMID:Proteolytic processing, axonal transport and differential distribution of chromogranins A and B, and secretogranin II (secretoneurin) in rat sciatic nerve and spinal cord. 1005 53

Human neuroblastoma cell lines comprise cellular counterparts of normal differentiation phenotypes arising from the developing neural crest Three distinct cell types have been isolated from cell lines: N-type cells with properties of embryonic sympathoadrenoblasts, S-type cells resembling nonneuronal Schwannian/glial/melanoblastic precursors, and I-type stem cells that can differentiate into either N- or S-type cells. Sympathoadrenoblasts from the normal neural crest further differentiate into neuronal or neuroendocrine cells. In this study, we show that malignant N-type neuroblasts likewise can differentiate futher along these same pathways. Retinoic acid and forskolin induce a neuronalphenotype, denoted morphologically by cell aggregation and increased neurite formation and biochemically by increases in neurofilament proteins, tyrosine hydroxylase, and secretogranin II and decrease inchromogranin A. By contrast, dexamethasone, a synthetic glucocorticoid, induces a chromaffin cell phenotype characterized by increased cell flattening, loss of neuritic processes, increased chromogranin A and tyrosine hydroxylase proteins, and decreased amounts of secretogranin II and neurofilaments. N-myc gene expression is upregulated by glucocorticoids; dexamethasone-treated N-type cells show significant (2.3- to 7.8-fold) increases in N-myc mRNA and protein steady-state levels. This effect is specific for glucocorticosteroids, is blocked by addition of the steroid receptor antagonist RU486, and involves direct activation of the N-myc promoter. These findings are the first to show that glucocorticoids upregulate N-myc expression in human neuroblastoma cells.
 ...
PMID:Glucocorticoids induce neuroendocrine cell differentiation and increase expression of N-myc in N-type human neuroblastoma cells. 1239 56

EM66 is a novel secretogranin II-derived peptide present in chromaffin cells of the human adrenal gland. The aim of the present study was to investigate the possible occurrence of EM66 in benign and malignant pheochromocytomas. Immunohistochemical labeling using specific antibodies revealed intense staining in both benign and malignant tumors. Coincubation of pheochromocytoma slices with EM66 and tyrosine hydroxylase antibodies showed that the immunostaining was restricted to chromaffin cells. RIA experiments indicated that serial dilutions of extracts of benign and malignant tumors generated displacement curves that were parallel to those produced by recombinant EM66. RIA quantification revealed concentrations of EM66 immunoreactivity ranging from 3.2-210 ng/mg protein (median = 25.6 ng/mg protein) in benign pheochromocytomas, and from 2.9-6.3 ng/mg protein (median = 3.8 ng/mg protein) in malignant tumors. The EM66-like immunoreactivity contained in the pheochromocytoma extracts was characterized by HPLC analysis combined with RIA detection. All of the benign and malignant tumors examined exhibited a single immunoreactive peak coeluting with recombinant EM66. These data indicate that the secretogranin II-derived peptide EM66 is generated in human tumoral chromaffin tissue. The significant difference in EM66 concentrations observed between benign and malignant pheochromocytomas suggests that measurement of EM66 levels may help identifying patients with higher risk of progression of such tumors.
 ...
PMID:Identification of the secretogranin II-derived peptide EM66 in pheochromocytomas as a potential marker for discriminating benign versus malignant tumors. 1278 58

The transcription factor cAMP response element binding protein (CREB), a member of the basic region leucine zipper (bZIP) family of proteins, is the major cAMP response element (CRE) binding. Other bZIP proteins, including CREB2, activating transcription factor 2 (ATF2), or CAAT/enhancer binding protein (C/EBP) have been reported to transactivate CRE-containing genes or to interfere with transactivation by CREB. We have designed a simple transactivation assay using expression of either a constitutively active CREB mutant or a nuclear targeted mutant of the catalytic subunit of cAMP-dependent protein kinase. In both cases, a striking stimulation of transcription of CRE-containing reporter genes was observed in noradrenergic locus coeruleus-like CATH.a cells. In addition, a constitutively active mutant of ATF2 specifically transactivated a secretogranin II promoter/luciferase reporter gene, but had no effect on the tyrosine hydroxylase promoter. In contrast, CREB2 and C/EBPalpha did not transactivate CRE-containing reporter genes, indicating that these bZIP proteins target distinct genetic elements. Experiments involving dominant-negative bZIP mutants revealed that CREB does not heterodimerize with CREB2, ATF2, c-Jun or C/EBP. Rather, CREB and ATF2 compete for binding to the CRE, and are independently able to up-regulate transcription of genes containing CRE motifs in their regulatory regions.
 ...
PMID:Role of basic region leucine zipper transcription factors cyclic AMP response element binding protein (CREB), CREB2, activating transcription factor 2 and CAAT/enhancer binding protein alpha in cyclic AMP response element-mediated transcription. 1566 80

The immunocytochemical development of the thoracolumbar sympathetic ganglion and its adrenal counterpart was studied in the chick from days 3.5 to 12 of incubation, using antibodies to 17 separate antigens, including antibodies to pan-neuroendocrine markers, catecholamine-synthesizing and proprotein-processing enzymes, and neuropeptides. Some of the antigens studied (Go protein-alpha subunit, thyrosine hydroxylase, and galanin) were strongly expressed from the first days of development, whereas others (chromogranin-A, chromogranin-B, 7B2 protein, and somatostatin) showed a diverse immunoreactive expression at different stages. Three different patterns were found in the development of both adrenal medulla and thoracolumbar sympathetic ganglion. In the first (chromogranin-A and B, Go protein-alpha subunit, tyrosine hydroxylase, HNK-1, and galanin), virtually all medullary and thoracolumbar sympathetic ganglion cells were strongly immunostained from day 4 onward. Except for HNK-1, chromogranin-A and B, there was a steady increase in immunoreactive cells for all the remaining antigens up to day 12. In the second (7B2 protein, proprotein convertase 2, and secretogranin II), full antigenic expression was reached in medullary and thoracolumbar sympathetic ganglion cells by day 10. In the third pattern (proprotein convertase 3, somatostatin, dopamine-beta-hydroxylase, neuron-specific enolase, vasoactive intestinal polypeptide, and met-enkephalin), differences in immunoreactivity were observed between the medullary and thoracolumbar sympathetic ganglion cells.
 ...
PMID:Immunocytochemical developmental patterns of the thoracolumbar sympathetic chain in the chick and a comparison with its adrenal counterpart. 1573 41


1 2 Next >>