Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0155339 (Brown)
12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A full-length genomic clone for human tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase, EC 1.14.16.2) has been isolated. A human brain genomic library constructed in EMBL3 was screened by using a rat cDNA for tyrosine hydroxylase as a probe [Brown, E. R., Coker, G. T., III, & O'Malley, K. L. (1987) Biochemistry 26, 5208-5212]. Out of one million recombinant phage, one clone was identified that hybridized to both 5' and 3' rat cDNA probes. Restriction endonuclease mapping. Southern blotting, and sequence analysis revealed that, like its rodent counterpart, the human gene is single copy, contains 13 primary exons, and spans approximately 8 kilobases (kb). In contrast to the rat gene, human tyrosine hydroxylase undergoes alternative RNA processing within intron 1, generating at least three distinct mRNAs. A comparison of the human tyrosine hydroxylase and phenylalanine hydroxylase [DiLella, A. G., Kwok, S. C. M., Ledley, F. D., Marvit, J., & Woo, S. L. C. (1986) Biochemistry 25, 743-749] genes indicates that although both probably evolved from a common ancestral gene, major changes in the size of introns have occurred since their divergence.
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PMID:Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5' alternative splice sites responsible for multiple mRNAs. 289 28

The activity of choline acetyltransferase is over twice as high in the hippocampus of Wistar Kyoto (WKY) than in Brown Norway (BN) rats, and this is paralleled by a comparable difference in acetylcholinesterase staining intensity within the hippocampal formation. However, the size of the whole hippocampus is smaller in WKY than in BN rats. There are no strain differences in the activities of the neurotransmitter-synthesizing enzymes: tyrosine hydroxylase in the septum and glutamic acid decarboxylase in the hippocampus. The findings indicate the existence of strain-dependent inverse relationship between the septo-hippocampal cholinergic system and the size of the hippocampus.
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PMID:Stain-dependent differences between the septo-hippocampal cholinergic system and hippocampal size. 611 23

The effects of adaptation to stress and of genetic differences on levels of in vitro tyrosine hydroxylase (TH) activity and in vivo catecholamine (CA) release are reviewed. It is shown that adaptation of animals to a wide variety of stressors including immobilization, electroconvulsive shock, footshock, hemorrhage, exercise and cold exposure results in a reduced CA response in the plasma, brainstem and heart to subsequent exposure to the same stress. Adaptation to many of the latter stressors also produces increased in vitro levels of TH activity. A similar inverse relation between in vitro TH activity and in vivo CA release is described for two inbred rat strains which differ in emotionality (Brown-Norway and Wistar Kyoto). The inverse relationship between TH activity and CA release may reflect different processes of biochemical adaptation utilized either for acclimation to stress, for preparation for emergency reactions or for changes in the metabolic costs of transmitter release. The similarity between environmental and genetic effects on these variables suggests that the above changes have a common adaptive function.
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PMID:Adaptation to stress: tyrosine hydroxylase activity and catecholamine release. 613 56

Tyrosine hydroxylase (TH) mRNA, immunoreactivity, and activity were examined as a reflection of dopamine expression in juxtaglomerular neurons intrinsic to the olfactory bulbs of young (6-month-old), middle aged (18-month-old), and aged (25- to 29-month-old) rats and mice. TH expression was maintained at levels observed in young animals in the olfactory bulbs of aged animals from two mouse strains, C57Bl/6JNia and C57Bl/6NNia, and one rat strain, an F1 hybrid between F344 and Brown Norway strains. The parental F344 rat strain exhibited reductions in TH expression of about 20% in 26- to 29-month-old animals as compared to 6- and 18 month-old rats. However, there was significant inter-animal variability. Some aged F344 rats had TH levels that were similar and others had activity levels that were 50% of those in young and middle aged animals. Neither the general condition of the animals nor the presence of adrenal tumors predicted the individuals with reduced TH expression. Olfactory bulb size, estimated from protein content, did not differ between rats and mice of different ages. In addition, expression of olfactory marker protein, a protein found primarily in mature olfactory receptor neurons, also was unchanged indicating the maintenance of afferent innervation. These data suggest that, in contrast to other brain dopamine systems, the expression of the dopamine phenotype is maintained in the aging olfactory bulb.
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PMID:Expression of tyrosine hydroxylase in the aging, rodent olfactory system. 777 30

Human TRP-1 has been immunopurified from normal human melanocytes cultured from black neonatal subjects and used to investigate the catalytic function of TRP-1 for the two substrates, L-tyrosine and L-DOPA. Immunopurified TRP-1 did not demonstrate DOPA staining on SDS/PAGE nor DOPA oxidase (DO) activity with either routine or modified assays. The purified TRP-1 also demonstrated no tyrosine hydroxylase (TH) activity using the routine Pomerantz assay. However, there was apparent TH activity exhibited by immunopurified TRP-1 under conditions with low tyrosine concentration (< or = 0.8 microCi/ml of 3H-tyrosine), prolonged incubation time (i.e., overnight) and in the absence of the cofactor L-DOPA. Using these latter specific conditions, TH activity was also detected in cell lysates from a tyrosinase-negative albino melanocyte line which exhibited no TH activity with the routine Pomerantz assay. In addition, TH activity under low substrate assay conditions was not exhibited in a melanocyte line derived from a TRP-1 deficient, Brown albino individual. However, the absence of TH in this Brown albino cell line could be compensated for by the addition of L-DOPA to the assay. These results suggested that TRP-1 has some tyrosine hydroxylase but no DOPA oxidase activity. We propose that one function of TRP-1 is to modulate tyrosinase activity by making DOPA available as a cofactor to perpetuate the initial steps in melanogenesis.
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PMID:Human TRP-1 has tyrosine hydroxylase but no dopa oxidase activity. 797 45

Most types of human oculocutaneous albinism (OCA) result from mutations in the gene for tyrosinase (OCA1) or the P protein (OCA2), although other types of OCA have been described but have not been mapped to specific loci. Melanocytes were cultured from an African-American with OCA, who exhibited the phenotype of Brown OCA, and his normal fraternal twin. Melanocytes cultured from the patient with OCA and the normal twin appeared brown versus black, respectively. Melanocytes from both the patient with OCA and the normal twin demonstrated equal amounts of NP-40-soluble melanin; however, melanocytes from the patient with OCA contained only 7% of the amount of insoluble melanin found from the normal twin. Tyrosinase- related protein-1 (TRP-1) was not detected in the OCA melanocytes by use of various anti-TRP-1 probes. Furthermore, transcripts for TRP-1 were absent in cultured OCA melanocytes. The affected twin was homozygous for a single-bp deletion in exon 6, removing an A in codon 368 and leading to a premature stop at codon 384. Tyrosine hydroxylase activity of the OCA melanocytes was comparable to controls when assayed in cell lysates but was only 30% of controls when assayed in intact cells. We conclude that this mutation of the human TRP-1 gene affects its interaction with tyrosinase, resulting in dysregulation of tyrosinase activity, promotes the synthesis of brown versus black melanin, and is responsible for a third genetic type of OCA in humans, which we classify as "OCA3."
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PMID:Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as "OCA3". 865 Dec 91

Rats were injected unilaterally with 6-hydroxydopamine either in the medial forebrain bundle or in the dorsolateral substantia nigra. Another group was injected unilaterally with kainate in the striatum. The loss of neurons was assessed by a reduction in tyrosine hydroxylase-like immunoreactivity for dopaminergic neurons, and choline acetyltransferase-like and glutamate decarboxylase-like immunoreactivities for cholinergic and GABAergic neurons, respectively. Brain sections also were analysed by autoradiography on 20 micron sections with the radio-iodinated serotonin-4 receptor antagonist [125I]SB 207710 [Brown A. M. et al. (1993) Br. J. Pharmac. 110, 10P]. Kainate injections in the striatum resulted in loss of choline acetyltransferase- and glutamate decarboxylase-like immunoreactive cell bodies in this area. There was also a decrease in glutamate decarboxylase-like immunoreactivity on the ipsilateral side in the substantia nigra and entopeduncular nucleus. These changes were accompanied by substantial (> 50%) decreases in [125I]SB 207710 binding in both the ipsilateral striatum (confined to the lesioned area) and substantia nigra, with no change in either the nucleus accumbens or the globus pallidus. There was also significant loss of [125I]SB 207710 binding in the ipsilateral entopeduncular nucleus. 6-Hydroxydopamine lesions placed either in the medial forebrain bundle or in the substantia nigra failed to decrease [125I]SB 207710 binding in any of these areas, although there was total loss of tyrosine hydroxylase-like immunoreactive terminals in the striatum and cell bodies in the nigra. We conclude that serotonin-4 receptors are present on projection neurons, both on their perikarya in the striatum and terminals in the nigra and entopeduncular nucleus. It is likely that these receptors are located on the GABAergic projection neurons and possibly on cholinergic and GABAergic interneurons. However, serotonin-4 receptors are not located on dopaminergic neurons, either on their cell bodies in the substantia nigra or terminals in the striatum.
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PMID:Localization of serotonin-4 receptors in the striatonigral pathway in rat brain. 884 4

In order to study the genetic factors involved in the neuroendocrine responses to stress, we have compared the intensity of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system activation following a 60 minute-restraint stress or after a 10 minute-exposure to a novel environment in three rat strains : outbred Wistar, inbred Brown Norway and Fischer 344, and F1 hybrid Brown Norway x Fischer 344 rats. The basal activity of the HPA axis did not differ between the four groups of rats whereas Brown Norway rats had the lowest release of corticosterone following restraint stress. Although differences in plasma adrenocorticotropic hormone failed to reach significance after exposure to a novel environment, the lowest level of corticosterone was found in Brown Norway rats. This lower release of corticosterone in Brown Norway rats has probably an adrenal origin as suggested by the ratios of corticosterone to ACTH levels following exposure to a novel environment: 632 +/- 222, 200 +/- 45, 636 +/- 89, 258 +/- 65 in Wistar, Brown Norway, Fischer 344 and F1 hybrids, respectively. This trait was dominant over the "adrenal responsive" phenotype of the Fischer 344 rat strain. In response to novelty, the lowest levels of prolactin and renin activity were found in plasma of Brown Norway and Wistar rats and the highest in Fischer 344 and F1 hybrid Brown Norway x Fischer 344 rats, the "high response" phenotype of the Fischer 344 strain being dominant. No strain-related difference was found in plasma glucose and either adrenal tyrosine hydroxylase or phenylethanolamine N-methyl transferase activity. Taken together, these data suggest that 1) genetic factors might contribute to the interindividual differences in neuroendocrine responses to stress and 2) subsets of these responses are controlled by specific genetic factors.
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PMID:Comparison of the neuroendocrine responses to stress in outbred, inbred and F1 hybrid rats. 967 42

Previously, we showed that 5-norbornene-2,2-dimethanol (5-NBene-2,2-DM) is an effective inducer of melanogenesis in cultured cells and guinea-pig skin [Brown et al. (1998) J. Invest. Dermatol., 110:428-437]. This study shows that 2,3-cis/exo-pinanediol (2,3-cs/ex-PinD) is a more effective inducer of melanogenesis than 5-NBene-2,2-DM in S91 mouse melanoma cells. Furthermore, 2,3-cs/ex-PinD appears to penetrate guinea-pig skin better than 5-NBene-2,2-DM and to induce higher levels of pigmentation. Both 5-NBene-2,2-DM and 2,3-cs/ex-PinD induce synthesis of nitric oxide (NO) in S91 cells, and the melanogenic activity of both compounds is reduced by inhibitors of the NO/cyclic guanosine monophosphate (cGMP)/protein kinase(PK) G signaling pathway, but not by inhibitors of the PKC or PKA pathways. Thus, these bicyclic monoterpene diols appear to induce melanogenesis by the same pathway in S91 cells as that shown previously for ultraviolet radiation in melanocytes (Romero-Graillet et al. (1996) J. Biol. Chem., 271:28052-28056). These compounds also induce NO synthesis, neurite outgrowth, and tyrosine hydroxylase activity in PC12 pheochromocytoma cells. Neurite outgrowth in PC12 cells is blocked by the guanylate cyclase inhibitor, LY83583 (6-anilino-2,8-quinolinequinone), indicating that, similar to S91 cells, the induction of morphological differentiation of PC12 cells by bicyclic monoterpene diols is regulated by a cGMP-dependent pathway.
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PMID:Bicyclic monoterpene diols induce differentiation of S91 melanoma and PC12 pheochromocytoma cells by a cyclic guanosine-monophosphate-dependent pathway. 1019 80

Decreased availability or efficacy of neurotrophic factors may underlie an increased susceptibility of mesencephalic dopaminergic cells to age-related degeneration. Neuregulins (NRGs) are pleotrophic growth factors for many cell types, including mesencephalic dopamine cells in culture and in vivo. The functional NRG receptor ErbB4 is expressed by virtually all midbrain dopamine neurons. To determine if levels of the NRG receptor are maintained during aging in the dopaminergic ventral mesencephalon, expression of ErbB4 mRNA and protein was examined in young (3 months), middle-aged (18 months), and old (24-25 months) Brown Norway/Fischer 344 F1 rats. ErbB4 mRNA levels in the substantia nigra pars compacta (SNpc), but not the adjacent ventral tegmental area (VTA) or subtantia nigra pars lateralis (SNl), were significantly reduced in the middle-aged and old animals when compared to young rats. Protein expression of ErbB4 in the ventral midbrain was significantly decreased in the old rats when compared to the young rats. Expression of tyrosine hydroxylase (TH) mRNA levels was significantly reduced in the old rats when compared to young animals in the SNpc, but not in the VTA or SNI. TH protein levels in the ventral midbrain were also decreased in the old animals when compared to the young animals. These data demonstrate a progressive decline of ErbB4 expression, coinciding with a loss of the dopamine-synthesizing enzyme TH, in the ventral midbrain of aged rats, particularly in the SNpc. These findings may implicate a role for diminished NRG/ErbB4 trophic support in dopamine-related neurodegenerative disorders of aging such as Parkinson's disease.
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PMID:Decreased expression of ErbB4 and tyrosine hydroxylase mRNA and protein in the ventral midbrain of aged rats. 1950 38


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