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)

The transsynaptic induction of tyrosine 3-monooxygenase (TH) in rat adrenal medulla is preceded by an early increase in the ratio of cyclic adenosine monophosphate (AMP) to cyclic guanosine monophosphate, an activation of cytosol cyclic AMP-dependent protein kinase, and a subsequent translocation of protein kinase catalytic subunits from cytosol to subcellular particles. As a result of this translocation, nuclear protein kinase activity increases during the induction of TH. Transection of splanchnic nerve reverts these events and prevents the induction of TH. Thus, adrenal medulla activation and translocation of cyclic AMP-dependent protein kinase may act as a long-range messenger for the genetic regulation of TH synthesis.
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PMID:Induction of tyrosine 3-monooxygenase in adrenal medulla: role of protein kinase activation and translocation. 0 36

We have previously shown that the phorbol ester, TPA, which activates protein kinase C, causes, in PC12 cells, a transcriptional activation of tyrosine hydroxylase (TH), the key enzyme in catecholamine synthesis. The study has now been extended to examine the processes that underlie this transcriptional stimulation and, in addition, to seek whether similar mechanisms are involved in long-term trans-synaptic induction of the TH gene in adrenal medullae of rats that have been given a single injection of reserpine. In both systems, it was found that the induction of c-fos gene transcription was associated with that of the TH gene but with different kinetics. The promoter of the TH gene contains (at position -207/-200) a sequence (TGATTCA) which differs from the consensus TRE or AP-1 site (TGACTCA) by one nucleotide. Experiments were carried out to investigate whether the AP-1 protein complex which is known to contain Fos and Jun binds to the putative TRE region of the TH promoter. In the gel shift assays, the nuclear protein extracts derived from TPA-treated PC12 cells and from AM of reserpine injected rats displayed a higher magnitude of binding to a 25-mer TRE-TH oligonucleotide as compared to controls. The results showed that the behaviour of TRE-TH was atypical in that two retarded complexes (A and B) were observed, which were displaced by specific competitors. Trans-activation experiments with plasmids TRE-TH/TK/CAT and -754/-19 TH/pUC18-CAT in PC12 cells showed an increase in CAT activity in response to TPA that correlates with the previously observed increase in TH transcriptional activity by TPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:AP-1 complex and c-fos transcription are involved in TPA provoked and trans-synaptic inductions of the tyrosine hydroxylase gene: insights into long-term regulatory mechanisms. 138 60

The discovery of immediate early genes (IEG) has provided neuroscientists with a new functional mapping technique. Labelling of neural tissue for the protein product of IEG provides an activity map with single-cell resolution. When combined with labelling for the chemical identity of the neuron, this provides a powerful tool for the investigation of specific cell populations along a neuraxis. Here we describe in detail a method which allows simultaneous bright-field visualization of neurochemically identified cells displaying increased IEG expression. This technique is evaluated in tissue from rats subjected to stimuli known to induce the expression of the IEG c-fos in various medullary catecholaminergic and hypothalamic neurosecretory cell groups. A 2-colour immunoperoxidase technique was used to visualize Fos, the nuclear protein product of c-fos, and the cytoplasmic antigens tyrosine hydroxylase (TH), phenylethanolamine N-methyl transferase (PNMT), oxytocin (OT) and vasopressin (VP). This involved simultaneous application of primary antibodies raised in different species followed by sequential application of appropriate biotinylated secondary antibodies and the avidin-biotin-peroxidase technique. Fos was visualized with nickel-intensified diaminobenzidine (Ni-DAB) in the first sequence while TH, PNMT, OT or VP were visualized with DAB alone, resulting in readily distinguishable black and amber reaction products, respectively. This dual immunoperoxidase technique is time saving compared to techniques using sequential application of primary antibodies and avoids the disadvantages associated with fluorescence techniques.
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PMID:Neurochemical identification of fos-positive neurons using two-colour immunoperoxidase staining. 810 Jun

Expression of the gene encoding the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT) is regulated by hormonal and neural stimuli. Because the 5'-upstream regions of the PNMT do not contain sequences analogous to those demonstrated to convey neural regulation to the tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) catecholamine-synthesizing enzyme genes, functional and biochemical analyses have been utilized to characterize PNMT promoter responses to cholinergic and depolarizing agents. In primary cultures of bovine adrenal medullary chromaffin cells, reporter gene expression from transiently transfected 3- and 0.9-kb-containing PNMT promoter constructs is stimulated approximately twofold by nicotine and muscarine. Depolarizing concentrations of K+ produce fourfold increases in expression. These responses are not detected with constructs containing the proximal 0.3-kb promoter, indicating that the regions between -273 and -877 bp convey neural responsiveness for the PNMT gene in bovine chromaffin cells. Electrophoretic mobility shift assays (EMSAs) with oligonucleotides encoding these regions of the PNMT promoter revealed distinctions in migration of nuclear protein complexes formed following treatment of chromaffin cells with nicotine, muscarine, or 50 mM K+. Thus, the PNMT promoter between 0.3 and 0.9 kb contains sequences capable of responding to cholinergic and depolarization stimuli. Moreover, these treatments influence the interactions of specific nuclear proteins with this region of the PNMT promoter.
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PMID:Neural regulation of phenylethanolamine N-methyltransferase (PNMT) gene expression in bovine chromaffin cells differs from other catecholamine enzyme genes. 1063 70

Previous studies have shown the presence of neuronal perikarya in the primate ovary, but not in the ovary from Sprague-Dawley rats. We report here that while such intrinsic neurons are indeed absent in this strain of rats, they can be visualized in the ovary from Wistar rats. The neurons, identified by their morphology and by the expression of NeuN (a neuron-specific nuclear protein), were detected at all postnatal intervals examined, from 14 h after birth to 50 days of age. While they were present in the ovarian hilum and medulla at all ages studied, neurons first appeared in the ovarian cortex during the juvenile period (postnatal days 10-20). In all cases, the size of the neuronal soma increased significantly during prepubertal development, reaching maximal values before puberty. Some neurons were catecholaminergic, as indicated by their content of immunoreactive tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. Some showed neuropeptide Y (NPY) immunoreactivity. TH-positive neurons were seen either in isolation or clustered in ganglion-like structures in both the ovarian cortex and medulla. These results indicate that ovarian neurons are not present in all strains of rats, but when present, the chemical phenotype of some of them is of a sympathetic nature, similar to that described in primates.
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PMID:Intrinsic neurons in the rat ovary: an immunohistochemical study. 1080 74

Reports that food intake is stimulated by fourth ventricular administration of glucose antimetabolites or uptake inhibitors suggest that glucose deprivation within the periventricular caudal brainstem activates compensatory neural mechanisms that restore global metabolic stasis. In the present study, Fos immunocytochemistry was employed to characterize the distribution of neurons within this region of the male rat brain that undergo genomic activation in response to intraventricular delivery of the antiglycolytic agent, 2-deoxy-D-glucose (2DG). Fos immunoreactivity (-ir) was only detected in the locus coeruleus (LC), nucleus of the solitary tract (NTS), and area postrema (AP) following drug treatment, whereas immunostaining for Fos was absent from these structures in the vehicle-treated control group. Dual-label immunocytochemical processing of sections of these loci for Fos- and tyrosine hydroxylase (TH)-ir revealed that, in each site, a majority of TH-ir-positive neurons were co-labeled for this nuclear protein in response to this treatment paradigm. These results provide evidence for the transcriptional activation of catecholaminergic neurons in discrete periventricular caudal brainstem structures during central glucopenia. Taken together with pharmacological evidence for the initiation of glucoprivic regulatory signaling within neural tissue accessible from the fourth ventricle, the present findings suggest that LC A6, NTS precommissural C2 and commissural A2, and AP TH-ir-positive neurons may function to monitor and/or signal alterations in periventricular glucose metabolism as a means of defending central substrate balance.
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PMID:Caudal brainstem Fos expression is restricted to periventricular catecholamine neuron-containing loci following intraventricular administration of 2-deoxy-D-glucose. 1098 89

The primate striatum contains tyrosine hydroxylase (TH)-immunoreactive (ir) neurons, the numbers of which are augmented after dopamine depletion. Glial cell line-derived neurotrophic factor (GDNF) strongly modulates the viability and phenotypic expression of dopamine ventral mesencephalic neurons. The effect of GDNF on TH-ir neurons intrinsic to the striatum has yet to be investigated. In the present study, stereological counts of TH-ir striatal neurons in aged and parkinsonian nonhuman primates revealed that GDNF delivered via a lentiviral vector (lenti-) further increased the number of these cells. Aged monkeys treated with lenti-GDNF displayed an eightfold increase in TH-ir neurons relative to lenti-beta-galactosidase-treated monkeys. Unilateral 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine treatment alone in young monkeys resulted in a bilateral eightfold increase in TH-ir striatal cells. This effect was further magnified sevenfold on the side of lenti-GDNF treatment. These cells colocalized with the neuronal marker neuronal-specific nuclear protein. Some of these cells colocalized with GDNF-ir, indicating that an alteration in phenotype may occur by the direct actions of this trophic factor. Thus, GDNF may mediate plasticity in the dopamine-depleted primate brain, which may serve to compensate for cell loss by converting striatal neurons to a dopaminergic phenotype.
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PMID:Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration. 1207 91

In the mammalian neocortex, neurons containing tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, constitute an enigmatic and ill-defined group of aspiny non-pyramidal cells. In the human neocortex, these neurons are mostly found in layers V-VI, the same layers in which another conspicuous group of nitrergic non-pyramidal cells are found - those containing nitric oxide synthase (nNOS) and that can be labeled by nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry. The main aim of the present study was to determine the extent to which neurons and fibers containing TH, NADPHd or nNOS co-localize in the human temporal cortex, using immunocytochemistry and NADPHd histochemistry. Furthermore, we have quantified the degree to which axons immunoreactive (ir) for TH contact the somata of neurons by co-labeling with the neuron-specific nuclear protein NeuN. As a result, we show that the population of TH-ir neurons can be subdivided into two main neurochemical groups: those expressing nNOS (26%) and those that do not (74%). There was no co-localization of TH with nNOS in the prominent horizontally oriented plexus of fibers in layer I and we did not observe any double bouquet cells, chandelier cells or basket cells that contained TH. Finally, we observed that only 6% of the TH-ir axonal boutons examined (n = 1724) could be seen to contact neuronal somata. Thus, most TH-ir axons must form synapses with dendrites. In conjunction with data from previous studies, these results suggest that TH is found in different neurochemically defined subpopulations of non-pyramidal neurons in layers V-VI of the human temporal cortex. Consequently, it appears that a partial overlap of the catecholaminergic and nitrergic systems is probably due to the intrinsic cortical TH-nNOS-ir neurons.
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PMID:Different populations of tyrosine-hydroxylase-immunoreactive neurons defined by differential expression of nitric oxide synthase in the human temporal cortex. 1257 Nov 19

Human neural stem cells have exhibited a remarkable versatility to respond to environmental signals. Their characterization in models of neurotoxic injury may provide insight into human disease treatment paradigms. This study investigates the survival and migration of transplanted human stem cells and tyrosine hydroxylase immunoreactivity in the parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model, using antisera recognizing human nuclear protein (hNuc) and tyrosine hydroxylase (TH). Our results indicate long-term (up to 90 days) survival of human stem cell xenograft in the MPTP-lesioned mouse and the presence of hNuc-immunoreactive cells at sites distal to the transplant core. Few TH-positive cells are identified in the striatum by immunoperoxidase staining and using immunofluorescent double labeling, infrequent TH-immunoreactive, transplanted cells are identified.
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PMID:Human neural stem cell transplantation in the MPTP-lesioned mouse. 1270 33

We sought an in vitro primate model for serotonin neurons. Rhesus monkey embryonic stem (ES) cell colonies were isolated and differentiated into embryoid bodies (EBs), then transferred to serum-free medium with 1% insulin-transferrin-selenium for 7 days to induce neural precursor cell (NPC) formation. NPCs were cultured in medium with 1% N-2 neural supplement and human fibroblast growth factor 2 (FGF2, 10 ng/ml) for 7 days to stimulate cell proliferation. Lastly, NPCs were dispersed into single cells and cultured without FGF2 for another 7 days to obtain terminal differentiation. Terminal cells were characterized for neuronal and serotonergic markers. Over 95% of the NPCs were immunopositive for nestin and Musashi1. Terminally differentiated cells appeared in both small and large morphologies. Most (>95%) of the mature cells (both small and large) were immunopositive for neuron-specific nuclear protein (NeuN), synaptophysin, microtubule-associated protein (MAP2C), Tau-1, neurofilament 160 (NF-160), beta-tubulin (TujIII), tryptophan hydroxylase (TPH), serotonin, the serotonin reuptake transporter (SERT), estrogen receptor-beta (ERbeta), and progestin receptor (PR), but not estrogen receptor-alpha (ERalpha). Less than 2-3% of cells were positive for tyrosine hydroxylase (TH). Reverse transcriptase polymerase chain reaction (RT-PCR) detected mRNA transcripts for TPH-1, TPH-2, SERT, 5-HT1A-autoreceptor, ERbeta, and PR in the differentiated population. A low level of expression of ERalpha mRNA was also detected. Quantitative RT-PCR indicated that the relative abundance of TPH-2 mRNA was greater than TPH-1 mRNA. Serotonin as measured by ELISA increased 3-fold in the mature stage compared to the selection and expansion stages. In summary, a remarkably high percentage of cells derived from monkey ES cells exhibited neuronal plus serotonergic markers as well as nuclear steroid receptors similar to primate CNS serotonin neurons, suggesting that these cells may serve as a useful primate model for serotonergic neurons.
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PMID:Serotonin neurons derived from rhesus monkey embryonic stem cells: similarities to CNS serotonin neurons. 1524 35


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