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)

In situ hybridization histochemistry, Northern blot analysis and immunohistochemistry were used to examine tyrosine hydroxylase (TH) mRNA concentrations and immunoreactivity in the locus coeruleus and cerebellum of the tottering (tg/tg), leaner (tgla/tgla), compound heterozygous (tg/tgla) and wild type control (+/+) mice, bred on a C57BL/6J background. Cerebellar Purkinje neurons, long considered to be GABAergic, showed high levels of TH mRNA in the caudal vermis and the lateral hemispheres of the cerebellum of tg/tg, tg/tgla, and tgla/tgla mice. Analysis of grain density over individual Purkinje cells showed significantly greater concentrations of TH mRNA in tg/tg, tg/tgla, and tgla/tgla mice as compared to +/+ wild type control mice. Comparison of adult (greater than or equal to 2 months) and young, pre-seizure (less than or equal to 3 weeks) mutant mice showed Purkinje cells densely labelled for TH mRNA at both ages, suggesting that TH gene expression in Purkinje cells is independent of the onset of seizures. Northern blot analysis confirmed the findings from the in situ hybridization studies, demonstrating a single band identical to TH mRNA. Immunohistochemistry confirmed the presence of TH protein in Purkinje cells of the caudal vermis and the lateral hemispheres of the cerebellum in both control and mutant mice. Quantitation of mRNA for TH and the coexisting neuropeptide, galanin, in the locus coeruleus detected no significant differences between adult tg/tg, tg/tgla and +/+ control mice. The present findings demonstrate that the classically GABAergic Purkinje cells in the cerebellum express low levels of TH, and that the mutant tottering and leaner strains of mice express extremely high levels of mRNA and protein for TH.
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PMID:Expression of tyrosine hydroxylase in cerebellar Purkinje neurons of the mutant tottering and leaner mouse. 127 53

The possibility that vasoactive intestinal polypeptide (VIP) may facilitate the nicotine-mediated induction of adrenal medullary tyrosine hydroxylase (TH) was investigated with primary cultures (5-7 days in vitro) of bovine adrenal chromaffin (BAC) cells. Exposure of BAC cells to 100 microM nicotine led to only a marginal increase in the amount of TH mRNA, TH protein, and TH activity. VIP, alone or in the presence of a phosphodiesterase inhibitor, produced a marked increase in TH mRNA, TH protein, and TH activity. Moreover, VIP together with nicotine, at concentrations that alone were devoid of effect, increased the amount of TH mRNA and TH activity. A synergistic effect of VIP and nicotine on cAMP accumulation in BAC cells was also apparent. The marginal effects of large doses of nicotine on both cAMP accumulation and TH induction were blocked completely by hexamethonium but were also partially inhibited by the VIP antagonist [p-chloro-D-Phe6,Leu17]-VIP. Nicotine may, therefore, stimulate the release of VIP from cultured BAC cells and VIP, in turn, by increasing cAMP, may synergize with nicotine to enhance TH gene expression.
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PMID:Vasoactive intestinal polypeptide facilitates tyrosine hydroxylase induction by cholinergic agonists in bovine adrenal chromaffin cells. 134 40

Previous studies have demonstrated that the sympathetic hypogastric ganglia (HG) are dependent upon the continued presence of testosterone for normal development and maintenance of tyrosine hydroxylase (TH) activity. The regulation of TH by testosterone has been examined further to determine whether the reduction in TH activity following castration is associated with changes in levels of TH protein and mRNA. TH protein was measured by immunotitration of HG homogenates using a TH-specific antibody, and TH-specific mRNA was detected by hybridization of dot blots of total RNA isolated from HG with a cDNA probe coding for TH. The results show that tyrosine hydroxylase activity, protein and mRNA are coordinately reduced in a graded fashion at 1, 2 and 4 weeks following castration. Testosterone replacement therapy immediately following castration prevents the decrease in TH levels. The results indicate that gonadal steroids regulate the biosynthesis of TH in the HG. Testosterone may control TH either directly by interacting with neurons of the HG, or indirectly by altering levels of trophic factors in the target tissues.
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PMID:Molecular aspects of the regulation of tyrosine hydroxylase by testosterone. 135 56

Isolated bovine adrenal chromaffin cells were used to study the nicotinic regulation of tyrosine hydroxylase (TH) gene expression. Continuous exposure of the cells to carbachol or the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) produces a time- and concentration-dependent increase in TH enzyme activity, whereas muscarine has no effect. DMPP at 1 microM (EC50 = 0.3 microM) elicits a two- to threefold elevation of both TH activity and TH immunoreactive protein level after 3-5 days in the presence of 2.5 mM calcium; the increase in enzyme levels is significantly less at lower extracellular calcium levels. The rate of hydroxylation of tyrosine to dopamine (DA) in intact cells, an index of endogenous TH activity, increases in parallel with the rise in TH levels. The TH mRNA level is elevated before the increase in protein levels. As determined by nuclear run-on assays, TH gene transcription is stimulated two- to threefold within 30 min of addition of 1 microM DMPP to the cells; transcription returns to basal levels by 2 h. Nitrendipine (20 microM) blocks the stimulation of transcription by DMPP. Pretreatment of the cells with cycloheximide (5 microM) does not prevent the DMPP stimulation of transcription. Forskolin (10 microM) also increases TH transcription (fourfold in 15 min) by a mechanism that is not blocked by cycloheximide. These results show that nicotinic receptor stimulation increases TH mRNA synthesis, TH protein levels, and TH activity in a calcium-dependent manner. Furthermore, the nicotinic influence on TH gene expression does not appear to require the synthesis of a protein factor for its effects. That in situ DA synthesis rates are elevated consequent to the rise in TH levels demonstrates that TH induction serves as a mechanism for enhancing the catecholamine-synthesizing capacity of the chromaffin cell on a long-term basis.
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PMID:Nicotinic cholinergic regulation of tyrosine hydroxylase gene expression and catecholamine synthesis in isolated bovine adrenal chromaffin cells. 135 19

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.
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PMID:Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain neurons after neurotoxin lesioning: a model for neuron aging. 137 6

The localizations of carnosine, nerve growth factor (NGF) receptor and tyrosine hydroxylase (TH) were studied in the embryonic and postnatal rat olfactory bulb and epithelium by means of single- and double-immunostaining methods. Tyrosine hydroxylase ontogeny was also evaluated at the mRNA level by in situ hybridization. All these molecules were expressed in the olfactory bulb but with different developmental patterns and cellular localization: carnosine immunoreactivity is seen from embryonic day 17 in primary olfactory neurons scattered in the nasal cavity and in fibres projecting from them to the olfactory bulb. Nerve growth factor-receptor immunoreactivity associated with small glial-like cells is visible in some glomeruli starting from the second day of postnatal life. At postnatal day 10 NGF-receptor immunoreactivity is extended to all glomeruli. Periglomerular neurons expressing TH mRNA and protein are present prenatally and their number sharply increases during the early postnatal development. Double-staining methods show that TH and NGF-receptor immunoreactivity do not overlap in cell bodies and processes. In addition, NGF-receptor immunoreactivity is not colocalized with carnosine. These findings definitely exclude NGF-receptor expression in periglomerular and primary olfactory neurons, suggesting that at least part of NGF-receptor expression in the olfactory bulb is associated with glial cells. In addition, they provide the first immunohistochemical data on carnosine ontogeny and confirm at the mRNA level previous studies on the ontogeny of TH protein.
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PMID:Carnosine, nerve growth factor receptor and tyrosine hydroxylase expression during the ontogeny of the rat olfactory system. 137 8

A dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP), administered to a pregnant female was found to affect postnatally the catecholamine metabolism of the pups. MPTP (5 mg/kg body weight/day) was administered to pregnant C57 Black BYA mice daily for 7 days between the 12th and 18th day of gestation. Dopamine levels and tyrosine hydroxylase (TH) activity were measured in the whole brain from the pups sacrificed after birth. In MPTP-treated pups at 7 days of age, TH total activity (TH activity/brain) did not change (92% of the control value), while TH specific activity (TH activity/mg protein) was increased to 163% of that in control mice. Thus, TH homospecific activity (TH activity/mg TH protein) doubled compared to the control mice. At 28 days of age, both the total activity and the specific activity of TH in the brains of postnatal mice were reduced to 50% and 78% of the control, respectively. Dopamine concentration in the striatum was also reduced significantly. Reduction in the TH activity and dopamine concentration were also observed at the age of 12 weeks. These data suggest that the prenatal exposure to MPTP induced a prolonged reduction of TH activity in the brains of mice with a transient increase of TH homospecific activity during the postnatal period.
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PMID:Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in prenatal stage on the dopamine system in the postnatal mouse brain. 167 18

This study examined the effect of aging on the relative number of dopamine (DA) nerve terminals in human caudate nucleus, their content of tyrosine hydroxylase (TH) protein, and the relative abundance of TH monomers with different molecular weights. Preliminary studies on brain tissue cryopreservation, performed with rat striatum, indicated that intact synaptosomes can be prepared from fresh tissue slowly frozen in 0.32 M sucrose with 5% dimethyl sulfoxide and then thawed rapidly prior to synaptosome preparation. Synaptosomes were prepared in this manner from postmortem caudate nucleus tissue obtained from normal humans 1 month to 63 years of age. To determine the relative number of DA nerve terminals for each individual, dopaminergic synaptosomes were selectively labeled with a monoclonal antibody to TH and quantified by fluorescence-activated cell sorting. To determine the relative amount of TH protein for each individual, the concentration of TH protein in the same synaptosomal preparations was determined using immunoblots. Our results suggest that caudate TH levels plateau soon after birth and tend to remain relatively stable during aging, since no changes in either the relative number of TH-containing nerve terminals or the concentration of TH protein were found in subjects 15-63 years of age. In light of previous studies showing an age-related loss of DA cell bodies, these findings suggest that remaining DA neurons compensate to maintain caudate levels of TH protein and TH-containing nerve terminals. Immunoblot studies identified three forms of TH monomer (60.6, 61.7, and 65.1 kDa), indicating that mRNAs coding for high molecular mass forms of TH may be actively translated in human brain. No age-related differences in the relative abundance of these forms were found.
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PMID:Effect of aging on tyrosine hydroxylase protein content and the relative number of dopamine nerve terminals in human caudate. 167 41

Expression of neurotransmitter phenotype during development of the nervous system is determined by several micro-environmental factors including cell aggregation. In order to delineate the role of cell aggregation and nerve growth factor (NGF) in regulating catecholamine expression, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) mRNA levels were examined in PC12 cells at different cell densities with and without NGF treatment. Upon plating of PC12 cells from low density (0.3-1.0 x 10(5) cells/cm2) to high density (0.5-2.0 x 10(6) cells/cm2) TH mRNA levels increased 4-fold within 1 day and remained at this level for several days. In cells replated from high to low density, TH mRNA returned to original levels within 1 day. In addition to TH mRNA, TH protein and dopamine levels were also found to increase in high-density cultures. In contrast to the increase in TH mRNA, DBH mRNA decreased about 40% in cells plated from low to high density. Hence, cell density differentially regulated TH and DBH mRNA levels. Unlike cell density, NGF treatment led to a decrease in both TH and DBH mRNA levels. However, when NGF treated cells were replated from low to high density, TH and dopamine levels increased. Thus NGF did not alter the density dependent regulation of TH. Similarly, TH mRNA levels increased in F4 cells, a mutant PC12 cell line unresponsive to NGF, when plated from low to high density. DBH mRNA decreased to undetectable levels when NGF treated PC12 cells were plated to high density, demonstrating a synergetic effect of cell density and NGF treatment on DBH mRNA levels.
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PMID:The differential effects of cell density and NGF on the expression of tyrosine hydroxylase and dopamine beta-hydroxylase in PC12 cells. 168 6

Striatal dopamine (DA) and metabolite (DOPAC) levels in 8-, 21-, 52- and 104-week-old C57BL mice were compared with those in 11-week-old mice, 20 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. DA and DOPAC concentrations expressed relative to striatal wet weight did not change with age. In contrast, DA and DOPAC levels increased almost linearly when values were expressed relative to the proportion of remaining tyrosine hydroxylase-positive (TH+) SNc neurons, reaching a 5-7-fold increase per average remaining TH+ neuron by 104 weeks of age (corresponding to neuronal loss of 70%) relative to that found per average neuron in 8-week-old mice. DA and DOPAC levels per average remaining TH+ SNc neuron following MPTP increased for low doses (neuronal losses less than 42%) but decreased for higher doses (55 and 70% losses) but the DOPAC/DA ratio per SNc neuron increased and was 9-fold higher in the 300 mg/kg MPTP-treated animals in comparison to saline controls. Cytoplasmic TH protein (estimated by somal TH immunodensity) was increased by 45% in SNc somata from mice treated with 150 mg/kg MPTP in comparison to saline controls, and by 63% in 104-week-old mice in comparison to 8-week-old animals. This study provides evidence that an average surviving TH+ SNc neuron compensates for the age-related loss of other SNc neurons by increasing dopamine synthesis similar to younger SNc neurons surviving low levels of toxically induced damage and that the compensation may be in part mediated by increased synthesis of TH.
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PMID:Increased dopamine synthesis in aging substantia nigra neurons. 168 20


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