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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate cis-elements responsible for catecholaminergic (CAnergic) neuron-specific expression of the tyrosine hydroxylase (TH) gene, we produced lines of transgenic mice carrying 5.0-kb, 2.5-kb and 0.2-kb fragments from the 5'-flanking region of the human TH gene fused to a reporter gene, chloramphenicol acetyltransferase (CAT), and designated them as TC 50, TC 25, and TC 02, respectively, and reporter gene expression in transgenic mice was analyzed by CAT assay by immunocytochemistry with anti-CAT antibody. High-level CAT expression was observed in the brain and adrenal gland using the 5.0-kb promoter of the TC 50 mice, but ectopic expression was consistently observed in several somatic tissues, e.g. thymus, colon, and testis. In brain, expression was achieved in CAnergic neurons with the largest construct (5.0 kb), but not with 2.5 kb or 0.2 kb of 5' flanking sequence. However, TC 50 mice also expressed CAT immunoreactivity in non-CAnergic neurons. In the TC 25 line CAT immunoreactivity was detected only in some non-CAnergic neurons. In the TC 02 line no CAT immunoreactivity was detected in any of the tissues examined. These results indicate that the 5.0-kb DNA fragment of the TH gene upstream region contains activity to express CAT in CAnergic neurons and surprisingly, lacks some regulatory elements attenuating ectopic expression, and that the 2.5-kb and 0.2-kb fragment are not sufficient for the proper expression. We discuss the presence of the tissue-specific regulatory elements in the structure portion of the TH gene and/or 3'-flanking region.
Brain Res Mol Brain Res 1992 Dec
PMID:Analysis of the human tyrosine hydroxylase promoter-chloramphenicol acetyltransferase chimeric gene expression in transgenic mice. 136 28

Slow neuron regression develops during the adult phase of life in select brain systems of mammals. We describe a model in adult rats that resolves several phases in a slow atrophic process that differentially influences levels of mRNA and protein for tyrosine hydroxylase (TH). Responses of striatal dopaminergic markers to 6-hydroxydopamine (6-OHDA) lesions in rats indicated that the striatal terminals maintained TH protein, despite greater than 3-fold loss of TH mRNA in the substantia nigra pars compacta (SNC) cell bodies whose axons project to the striatum. The loss of TH mRNA/cell was progressive up to 9 months, whereas SNC cell body shrinkage stabilized by 3 months post-lesioning. Consideration of possible mechanisms in protein turnover motivated a search for PEST motifs in the TH of rats and other vertebrates that could be a point of regulation by altering the rate of TH protein turnover.
Brain Res Mol Brain Res 1992 Mar
PMID:Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain neurons after neurotoxin lesioning: a model for neuron aging. 137 6

The normal complement of neurotransmitters in noradrenergic neurons was altered by expressing the structural gene for the enzyme phenylethanolamine-N-methyltransferase (PNMT) under the control of the dopamine-beta-hydroxylase gene promoter in transgenic mice. This resulted in accumulation of large amounts of epinephrine in neurons of the sympathetic nervous system (SNS) and central nervous system (CNS) but did not reduce norepinephrine levels. Adrenalectomy reduced PNMT levels in the SNS and CNS, suggesting that the transgene is positively regulated by adrenal steroids. Epinephrine levels were unaffected by this treatment in the CNS, suggesting that PNMT is not rate limiting for epinephrine synthesis. However, catecholamines were elevated in a sympathetic ganglion and a target tissue of the SNS, perhaps due to up-regulation of tyrosine hydroxylase in response to adrenalectomy. These transgenic mice also reveal a marked difference in the ability of chromaffin cells and neurons to synthesize epinephrine.
Mol Endocrinol 1992 Nov
PMID:Alteration of neurotransmitter phenotype in noradrenergic neurons of transgenic mice. 148 Jan 81

Trypsin proteolysis of tyrosine hydroxylase (TH) produces a 34-kDa fragment that is catalytically active but does not contain the regulatory phosphorylation sites. In this report, activation of TH by proteolysis was characterized further. Proteolysis results in a decrease in Kms for both substrate and cofactor. The increase in affinity for cofactor was identical to that produced by phosphorylation with cAMP-dependent protein kinase. Additionally, proteolysis of an N-terminal region containing the regulatory phosphorylation sites was sufficient to produce a decrease in Km for cofactor. Activation of substrate binding required more extensive proteolysis but also corresponded to N-terminal digestion. Moreover, this activation was coincident with a broadened substrate specificity. In combination, these data indicate that the N-terminus of tyrosine hydroxylase regulates cofactor binding and directs substrate specificity.
J Mol Neurosci 1991
PMID:Limited proteolysis of rat brain tyrosine hydroxylase defines an N-terminal region required for regulation of cofactor binding and directing substrate specificity. 167 92

The effects of the tetrodotoxin-insensitive Na+ channel activator palytoxin on both the secretion of endogenous catecholamines and the formation of 14C-catecholamines from [14C]tyrosine were examined using cultured bovine adrenal chromaffin cells. Palytoxin was shown to cause the stimulation of catecholamine secretion in a concentration-dependent manner. However, this toxin caused the reduction rather than the stimulation of 14C-catecholamine formation at the same concentrations. Palytoxin failed to cause any alteration in the activity of tyrosine hydroxylase prepared from bovine adrenal medulla. Furthermore, the uptake of [14C]tyrosine into the cells was shown to be inhibited by this toxin under the conditions in which the suppression of 14C-catecholamine formation was observed, and this inhibitory action on tyrosine uptake was closely correlated with that on catecholamine formation. The inhibitory action of palytoxin on tyrosine uptake into the cells was observed to be noncompetitive, and this effect was not altered by the removal of Na+ from the incubation mixture. These results suggest that palytoxin may be able to inhibit the uptake of [14C]tyrosine into the cells, resulting in the suppression of 14C-catecholamine formation, probably through its direct action on the plasma membranes of bovine adrenal chromaffin cells.
Mol Pharmacol 1991 Jul
PMID:Tetrodotoxin-insensitive Na+ channel activator palytoxin inhibits tyrosine uptake into cultured bovine adrenal chromaffin cells. 167 49

The administration of nicotine stimulates the transcription rate of the tyrosine hydroxylase gene in rat adrenal medulla. This stimulation occurs very rapidly (within 10 min) after the subcutaneous injection of nicotine and persists for at least 1 hr after a single injection of the drug. Repeated injections of the drug (seven injections once every 30 min) are associated with a more persistent activation of the gene (for at least 3 hr) and elicit the induction of tyrosine hydroxylase mRNA and tyrosine hydroxylase protein. Quantitatively, the increases in tyrosine hydroxylase gene transcription rate, mRNA, and protein are approximately equivalent. The effect of nicotine is dose dependent; a significant increase in tyrosine hydroxylase gene transcription rate is observed using 1.0 mg/kg nicotine, whereas 0.33 mg/kg nicotine produces no effect. The nicotinic receptor antagonists hexamethonium and mecamylamine partially inhibit the nicotine-mediated stimulation of the tyrosine hydroxylase gene. The lack of total blockade of the nicotine-mediated effect suggests that nicotine acting centrally may elicit the release of substances from the splanchnic nerve, that interact with receptors (other than the nicotinic receptor) that play a role in regulating the tyrosine hydroxylase gene. The administration of carbachol also stimulates rat adrenomedullary tyrosine hydroxylase gene transcription rate. The effect of carbachol is not inhibited by hexamethonium but is completely blocked by the muscarinic antagonist atropine. The muscarinic agonist bethanechol also stimulates this gene in rat adrenal medulla. Our results suggest that multiple receptors and signal transduction pathways are involved in the regulation of the tyrosine hydroxylase gene in the rat adrenal medulla.
Mol Pharmacol 1991 Aug
PMID:Stimulation of tyrosine hydroxylase gene transcription rate by nicotine in rat adrenal medulla. 167 51

We have examined the changes which occur in neuronal expression of tyrosine hydroxylase (TH) and proopiomelanocortin (POMC) mRNA in response to castration and hyperprolactinemia (HP) in male rats. Steady-state mRNA levels were determined by quantitative in situ hybridization histochemistry (ISHH) using 35S-labeled synthetic 48-base oligodeoxynucleotide probes. Castration produced a 27% increase in TH mRNA in the periventricular and arcuate nuclei. PRL-exposed rats exhibited a further 27% increase in the level of TH mRNA and a striking 48% increase in POMC mRNA in periarcuate region cell bodies. These results indicate that gonadal steroids and PRL are involved, either directly or indirectly, in regulating the biosynthesis of TH and POMC in the hypothalamus.
Brain Res Mol Brain Res 1991 Jun
PMID:Tyrosine hydroxylase and POMC mRNA in the arcuate region are increased by castration and hyperprolactinemia. 167 16

The presence of enzymes (tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (D beta H)) and enzymatic activities (monoamino oxidase, (MAO)) related to catecholamine synthesis and degradation have been investigated in cervical, thoracic and lumbar dorsal root ganglia (DRG) of adult male rats using immunohistochemical and enzyme histochemical techniques, respectively. A small population (between 2-4%) of TH-like immunoreactive and MAO positive neurons was found. They were small in diameter (18 +/- 2 microns), predominate in lumbar DRG and did not display D beta H-like immunoreactivity. These sensory neurons which are likely catecholaminergic were insensitive to systemic administration of capsaicin and 6-hydroxydopamine. Colchicine administration caused an increase of TH-like immunoreactivity and MAO activity. Pargyline produced an increase in TH-like immunoreactivity and the disappearance of MAO activity. The possible dopaminergic nature of the subpopulation of DRG sensory neurons investigated in the present study is discussed.
Cell Mol Biol 1991
PMID:Presence of catecholamine-related enzymes in a subpopulation of primary sensory neurons in dorsal root ganglia of the rat. 168 49

Isolation of adult animals represents a form of psychological stress from which the animals cannot escape. In order to assess the effect of this stressor on neurochemical substrates in the brain, we assessed behavior and measured tyrosine hydroxylase and proenkephalin mRNA levels in selected brain areas by in situ hybridization histochemistry. Tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (LC) were significantly and progressively increased by 18, 42 and 68% after 7, 14 or 28 days of isolation, respectively. TH mRNA in the midbrain was transiently increased by isolation. Levels were significantly elevated by 34 and 48% above group-housed controls in the ventral tegmentum and the substantia nigra, respectively, after 14 days of isolation. In the forebrain, proenkephalin (PE) mRNA levels were found to be transiently decreased by 29% in the anterior and medial aspects of the caudate-putamen and the nucleus accumbens after 7 or 14 days of isolation stress, but the levels returned toward control levels after 28 days of isolation. Behavioral tests indicate that isolated animals progressively became more aggressive with duration of stress and showed a small but significant decrease in locomotor activity. The results demonstrate that a physically noninvasive stressor such as isolation of adult male rats can produce significant alterations in brain neurochemistry. The neurochemical responses observed may represent a brain mechanism designed to help the organism adapt to or protect from the deleterious effects of chronic psychological stress.
Brain Res Mol Brain Res 1991 Oct
PMID:Isolation stress increases tyrosine hydroxylase mRNA in the locus coeruleus and midbrain and decreases proenkephalin mRNA in the striatum and nucleus accumbens. 168 31

Transient transfection of pLB2CAT constructs bearing short synthetic oligonucleotides derived either from the tyrosine hydroxylase (TH) promoter or other sources was used to examine functional cAMP regulatory element (CRE) activity in a variety of cell lines. The region containing only the putative TH CRE was found to be as or more effective in conferring cAMP responsiveness onto pLB2CAT (which employs the TK promoter) than the immediate 272 bp region of the TH promoter. Increases in CAT activity of 10- to 20-fold were observed in JEG-3 cells with a single insert of the TH CRE region (-31 to -54) in pLB2CAT, and the presence of a second insert generated only a modest further increase. This construct also responded to cAMP in 4 other cell lines tested but the degree of increase was less dramatic. Inserts containing the consensus 8 bp CRE motif embedded in other natural or artificial contexts served generally as weak functional CREs in all cell lines tested. In vitro analysis revealed that a specific protein-DNA complex apparently containing a single protein with a MW of 45-50 kDa was formed equally well with JEG-3 cell nuclear extract and CRE-bearing-TH and other fragments which produced dramatically different cAMP effects in vivo. These results suggest specificity in the effects of cAMP on different CREs which are dictated by contextual differences.
Brain Res Mol Brain Res 1991 Oct
PMID:Functional recognition of the neuronal tyrosine hydroxylase cAMP regulatory element in different cell types. 168 32


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