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)

The cellular localization of the enzymes tyrosine hydroxylase (TH), aromatic amino-acid decarboxylase (or dopa decarboxylase, DDC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla of adult rats and rat fetuses (14th, 17th, 18th, 19th and 21st day) was examined. In the prenatal stages the medullary blastema and an adjacent part of the primitive sympathetic trunk were also investigated. Tissues were fixed in ice-cold 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.2). Cryostat sections (10 micron in thickness) were stained by the indirect immunofluorescence technique. Rabbit antibodies to TH (isolated from human pheochromocytoma), DDC, DBH and PNMT (the latter three isolated from bovine adrenal medulla) were used. Sections incubated with serum of non-immunized rabbits were used as controls. In the adult adrenal medulla, two cell types can be distinguished. One cell type contains only TH, DDC and DBH. The other cell type contains PNMT in addition. It is concluded that these cells correspond to the noradrenaline-(NA-) and adrenaline- (A-)storing cells respectively. In all prenatal stages TH, DDC and DBH are found in the primitive sympathetic trunk, in the medullary blastema, and in the medullary cells which have migrated into the cortical "anlage". PNMT is observed for the first time on the 18th day. Moreover, PNMT could only be demonstrated inside the adrenal gland. From these observations it is concluded that the capacity to synthesize NA is developed even before the "medullary" cells have reached the cortical "anlage". On the contrary, the capacity to synthesize A seems to be acquired only after this contact is established. The hypothesis is put forward that this phenomenon might indicate the induction of PNMT by glucocorticoids secreted by the fetal cortex.
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PMID:Appearance of tyrosine hydroxylase, aromatic amino-acid decarboxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase during the ontogenesis of the adrenal medulla: an immunohistochemical study in the rat. 4 Jul

Catecholamine neurotransmitters--dopamine, noradrenaline (norepinephrine), adrenaline (epinephrine)--are synthesized in catecholaminergic neurons from tyrosine, via dopa, dopamine and noradrenaline, to adrenaline. Four enzymes are involved in the biosynthesis of adrenaline: (1) tyrosine 3-mono-oxygenase (tyrosine hydroxylase, TH); (2) aromatic L-amino acid decarboxylase (AADC, or DOPA decarboxylase, DDC); (3) dopamine beta-mono-oxygenase (dopamine beta-hydroxylase, DBH); and (4) noradrenaline N-methyltransferase (phenylethanolamine N-methyltransferase, PNMT). We cloned full-length complementary DNAs (cDNAs) and genomic DNAs of human catecholamine-synthesizing enzymes (TH, AADC, DBH, PNMT) and determined the nucleotide sequences and the deduced amino acid sequences. We discovered multiple messenger RNAs (mRNAs) of human TH, human DBH, and human PNMT. Four types (types 1, 2, 3, and 4) of human TH mRNAs are produced by alternative mRNA splicing mechanism from a single gene. We found the multiple forms of TH in two species of monkeys, but only a single mRNA corresponding to human TH type 1 in Sunkus murinus and rat, suggesting that the multiplicity of TH mRNA is primate-specific. Total TH mRNA, especially the most abundant type 2 and type 1 mRNAs in the human brain, were found to be reduced during the process of aging. The multiple forms of human TH may give additional regulation to the human enzyme, probably through altered phosphorylation and activation. We have succeeded in producing transgenic mice carrying multiple copies of the human TH gene in brain and adrenal medulla. The level of human TH mRNA in brain was about 50-fold higher than that of endogenous mouse TH mRNA. In situ hybridization demonstrated an enormous region-specific expression of the transgene in substantia nigra and ventral tegmental area. TH immunoreactivity in these regions, Western blot analysis, and TH activity measurements proved definitely increased TH in transgenic mice, though not comparable to the increment of the mRNA. However, catecholamine levels in transgenics were not significantly different from those in non-transgenics. The results suggest complex regulatory mechanisms for human TH gene expression and for the catecholamine levels in transgenic mice. Kohsaka and Uchida in collaboration with us applied genetically engineered (human TH cDNA-transfected) non-neuronal cells to brain tissue transplantation in parkinsonian rat models. We isolated and sequenced a full-length cDNA encoding human AADC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genes for human catecholamine-synthesizing enzymes. 168 50

Dopa decarboxylase (DDC; aromatic-L-amino-acid decarboxylase; aromatic-L-amino-acid carboxylase, EC 4.1.1.28) was purified from rat liver and its partial sequence was determined. Synthetic oligonucleotides were used to construct and screen rat liver cDNA libraries, and three clones were isolated and sequenced. The 2 kilobases of DDC cDNA cloned consisted of a 5'-noncoding segment of 78 nucleotides, a coding region of 1440 nucleotides, and a 3'-noncoding region of 438 nucleotides. The encoded protein of 480 amino acid residues had a molecular weight of 54,000. A special feature of the primary structure of rat DDC was a repeating structure consisting of 29 amino acid residues. A sequence of 58 amino acid residues, including this repeating structure of rat DDC, was found to show homologies with those of rat tyrosine hydroxylase, human dopamine beta-hydroxylase, and bovine phenylethanolamine N-methyltransferase, other mammalian enzymes that synthesize catecholamines. These results indicate that catecholamine biosynthetic enzymes are structurally related and suggest that their homologous domains are important for catechol-protein interactions.
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PMID:Molecular cloning and sequencing of a cDNA of rat dopa decarboxylase: partial amino acid homologies with other enzymes synthesizing catecholamines. 281 83

This experiment examined whether various catecholaminergic synthesis inhibitors and receptor blockers affect the inhibitory effect on the frequency of pulsatile luteinizing hormone (LH) secretion induced by local application of estradiol benzoate (EB) into the preoptic suprachiasmatic area (POSC) of ovariectomized rats. Ovariectomized rats were pretreated with either alpha-methyl-p-tyrosine (AMPT; tyrosine hydroxylase inhibitor), AMPT plus threo-dihydroxyphenylserine (DOPS; norepinephrine precursor), diethyldithiocarbamate (DDC; dopamine-beta-hydroxylase inhibitor), pimozide (dopaminergic receptor blocker), phenoxybenzamine (alpha-adrenergic receptor blocker), propranolol (beta-adrenergic receptor blocker), or their vehicles. EB implantation into the POSC reduced the frequency of existing pulsatile LH secretion in vehicle-treated rats. Pretreatment of the rat with AMPT, AMPT plus DOPS, or pimozide did not affect the basal pulsatile LH secretion but eliminated the suppressive effect of EB implantation on the LH pulse frequency. In rats pretreated with DDC or phenoxybenzamine, basal pulsatile LH secretion was significantly inhibited, and EB implantation did not lower serum LH further in these rats. Propranolol had no obvious effect on either basal pulsatile LH secretion or EB-induced suppression of LH pulse frequency. These findings suggest that, in addition to the alpha-adrenergic involvement in maintaining the basal pulsatile LH secretion, the intact dopaminergic system is required for the suppression of the frequency of LH pulses induced by estrogen.
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PMID:Dopaminergic involvement in the estrogen-induced suppression of frequency of pulsatile luteinizing hormone secretion in the ovariectomized rat. 301 66

We measured the levels of dopamine, tyrosine hydroxylase (TH) protein, and dihydroxyphenylalanine (DOPA) decarboxylase (DDC) protein in the striatum of 10 patients with idiopathic Parkinson's disease (PD) and 23 patients with dominantly inherited olivopontocerebellar atrophy (OPCA). The levels of dopamine were markedly reduced (2% of control) in the striatum of the patients with PD, whereas striatal dopamine in the patients with OPCA ranged from normal (> 60% of control) to moderately reduced (20-60% of control) to severely depleted (< 20% of control). Both TH and DDC protein levels were significantly lower than those of the controls in the striatum of all of the patients with PD and in the subgroup of patients with OPCA having severely depleted dopamine. In contradistinction, TH but not DDC protein levels were reduced in those patients with OPCA having moderately reduced dopamine levels. This suggests that in the early stage of nigrostriatal dopamine neurone degeneration, DDC levels may be less susceptible to neurodegenerative influences than is TH synthesis or, alternatively, DDC synthesis may be more aggressively upregulated. Unexpectedly, from the blot immunolabeling analysis an additional DDC-immunoreactive band of slightly lower apparent molecular mass was detected in two of the patients with PD and in 12 of the patients with OPCA. This additional DDC band, which was not present in any of the control subjects, may reflect posttranslational modification(s) of DDC related to the neurodegenerative process.
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PMID:Striatal dihydroxyphenylalanine decarboxylase and tyrosine hydroxylase protein in idiopathic Parkinson's disease and dominantly inherited olivopontocerebellar atrophy. 788 42

DOPA decarboxylase (DDC; aromatic-l-amino acid decarboxylase; EC 4.1.1.28) is absent in retinas from 6-day-old chicken embryos (E6) but is expressed in retina of E8 embryos, in the presumptive outer plexiform layer. Thereafter, DDC appears in cell bodies of presumptive amacrine cells. The dopamine (DA) content of E9/10 and E15/16 retinas, pre-incubated with l-DOPA for 1 h, increased 250- and 600-fold, respectively, showing that DDC is active since early in development. Intercellular communication, measured by endogenous cyclic AMP accumulation, was observed when retinas from E9/10 to E15/16 were pre-incubated for 1 h with 1 mm l-DOPA, washed and followed by incubation in the presence of 0.5 mm 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor. Cyclic AMP accumulation was prevented when pre-incubation with l-DOPA was carried out in the presence of carbidopa. Moreover, the accumulation of cyclic AMP was inhibited by SCH 23390 (2 micro m). The incubation of retinas in medium previously conditioned by retina-pigmented epithelium (RPE) also increased its cyclic AMP content with the characteristics described for l-DOPA. Our results show that dopaminergic communication takes place in the embryonic retina, before tyrosine hydroxylase expression, provided l-DOPA is supplied to the tissue. It also shows that RPE is a potential source of l-DOPA early in development.
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PMID:L-DOPA supply to the neuro retina activates dopaminergic communication at the early stages of embryonic development. 1280 23

The cuticles of most insect larvae have a variety of melanin patterns that function in the insects' interactions with their biotic and abiotic environments. Larvae of the armyworm Pseudaletia separata have black and white stripes running longitudinally along the body axis. This pattern is emphasized after the last larval molt by an increase in the contrast between the lines. We have previously shown that 3,4-dihydroxy-L-phenylalanine (Dopa) decarboxylase (DDC) is activated during the molt period by preferential enhancement of its transcription in the epidermal cells beneath the black stripes. This study demonstrated that tyrosine hydroxylase (TH) expression is activated synchronously with DDC. Furthermore, enhancement of DDC and TH transcription is due to an increase in cyotoplasmic Ca(2+), which is induced by the insect cytokine, growth-blocking peptide (GBP). Enhanced gene expression for both enzymes was induced by substitution of the calcium ionophore A23187, and completely blocked by EGTA. A GBP-induced increase in cytoplasmic Ca(2+) was seen in epidermal cells under the black stripes but not those beneath the white stripes, suggesting that a difference in Ca(2+) concentration in stripe cells leads to the specific expression of DDC and TH genes. Based on the fact that epidermal cells beneath the white stripes contain abundant granules composed mainly of uric acid, which can form a complex with Ca(2+) and hence decrease its free concentration, we discuss the possibility that uric acid, as well as GBP, contributes to the difference in cytoplasmic Ca(2+) within the epidermal cells.
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PMID:Insect cytokine, growth-blocking peptide, is a primary regulator of melanin-synthesis enzymes in armyworm larval cuticle. 1733 Nov 85

The dopaminergic system has been previously associated to behavioral facilitation and aggression, hence making the pathway a good candidate for suicidal behavior. We studied gene variants in the tyrosine hydroxylase (rs3842727, rs6356) and DOPA decarboxylase (rs1451371, rs1470750, rs998850) genes in a sample of 571 individuals consisting of 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide and 312 German control subjects. TH variants were not associated with suicide (uncorrected P = 0.023) and related traits. Some marginal associations could be observed for DDC with suicide, violence, anger, and aggression. In conclusion, our study does not support the involvement of TH gene variants as major contributors to suicide, whereas DDC variants could mediate some features related to suicide and be involved in violent suicidal behavior.
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PMID:Dopa decarboxylase and tyrosine hydroxylase gene variants in suicidal behavior. 1794 5

A neuropeptide hormone-signalling pathway controls events surrounding eclosion in Drosophila melanogaster. Ecdysis-triggering hormone, eclosion hormone and crustacean cardioactive peptide (CCAP) together control pre-eclosion and eclosion events, whereas bursicon, through its receptor rickets (RK), controls post-eclosion development. Cuticular tanning is a convenient visible marker of the temporally precise post-eclosion developmental progression, and we investigated how it is controlled by the ecdysis neuropeptide cascade. Together, two enzymes, tyrosine hydroxylase (TH, encoded by ple) and dopa decarboxylase (DDC, encoded by Ddc), produce the dopamine that is required for tanning. Levels of both the ple and Ddc transcripts begin to accumulate before eclosion, coincident with the onset of pigmentation of the pharate adult bristles and epidermis. Since DDC activity is high before the post-eclosion onset of tanning, a different factor must be regulated to switch on tanning. Transcriptional control of ple does not regulate the onset of tanning because ple transcript levels remain unchanged from 24 hours before to 12 hours after eclosion. TH protein present before eclosion is degraded, and no TH activity can be detected at eclosion. However, TH protein rapidly accumulates within an hour of eclosion and we provide evidence that CCAP controls this process. Furthermore, we show that TH is transiently activated during tanning by phosphorylation at Ser32, as a result of bursicon signalling. We conclude that the ecdysis hormone cascade acts as a regulatory switch to control the precise onset of tanning by both translational and activational control of TH.
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PMID:A neuropeptide hormone cascade controls the precise onset of post-eclosion cuticular tanning in Drosophila melanogaster. 1800 40

Growth-blocking peptide (GBP) is a 25 amino acid insect cytokine found in lepidopteran insects that has diverse biological activities, such as larval growth regulation, paralysis induction, cell proliferation, and stimulation of immune cells. GBP also enhances expression of the tyrosine hydroxylase (TH, EC 1.14.16.2) and 3,4-dihydroxy-l-phenylalanine (Dopa) decarboxylase (DDC, EC 4.1.1.26) genes, which elevate dopamine levels in insect epidermal cells. We used insect epidermis and cultured cells to define the role of the GBP signaling pathway in the enhancement of TH and DDC gene expression. It has been recently reported that robust expression of the DDC gene requires activation of extracellular signal-regulated kinase (ERK) in epidermal cells of wounded Drosophila embryos. This study confirmed that GBP activates ERK, but this activation is not directly linked to the enhancement of TH and DDC gene expression. One of the GBP pathway components is phospholipase C, whose activation is essential for the activation of ERK and elevation of expression of both enzyme genes. The downstream signaling pathways diverge to ERK activation through activated protein kinase C and expression of the enzyme genes through inositol triphosphate receptor-mediated Ca2+ influx from extracellular fluid. Our data indicate that the diverged GBP signaling pathways enable GBP to exert completely different biological functions, even in a single cell type.
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PMID:Insect cytokine growth-blocking peptide signaling cascades regulate two separate groups of target genes. 1821 68


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