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)

We investigated the proteome of the anterior pituitary gland (AP) in a species in which the genome has been sequenced. Subcellular fractions of APs from 2-month-old male mice were prepared for protein denaturation, treatment with trypsin and analyses utilizing micro liquid chromatography tandem mass spectrometry and the database search software SEQUEST. In the nuclear, non-nuclear 100,000 g and cytosolic fractions, we identified 49, 36 and 68 different proteins, respectively. A total of 115 distinct proteins were detected. We identified growth hormone, prolactin, pro-opiomelanocortin, the alpha-subunit for the glycoprotein hormones, and luteinizing hormone-beta. Groups of other identified proteins included hormone-processing, secretion granule-associated, non-hormonal endoplasmic reticulum-associated, calcium-binding, protein kinase C-associated, histones, non-histone chromosomal, other RNA-binding, heterogeneous nuclear ribonucleoproteins, splicing factors, helicases, lamins, ribosomal, microtubule-associated, microfilament-associated, adenosine triphosphate- and guanosine triphosphate-associated, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation, enzymes in glycolysis and the tricarboxylic and urea cycles and the pentose phosphate path, heat-shock, glutathione-associated, peroxidases, ubiquitin-associated, catabolic, protease inhibitors, other, and blood proteins. The 115 proteins reported in this study and the 145 proteins reported in a previous study on the AP of the adult male Golden Syrian hamster are compared and form a foundation for defining the proteome in normal adult male AP.
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PMID:Mouse anterior pituitary gland: analysis by ion trap mass spectrometry. 1610 33

Tyrosine 3-monooxygenase (tyrosine hydroxylase, TH) catalyzes the initial and rate-limiting step in the catecholamine biosynthesis. Alteration in TH activity is involved in the pathogenesis of certain disorders derived from catecholaminergic dysfunction. In the present review, we focus on recent advances in molecular genetic study of TH function and inherited diseases. Knockout mice lacking TH gene show severe catecholamine depletion and perinatal lethality. Mice heterozygous for the TH mutation exhibit defects in some neuropsychological functions. Dopamine-deficient mice impair motor control and operant learning during postnatal development. In addition, some point mutations in the human TH gene underlie the inherited diseases, including the recessive form of L-DOPA-responsive dystonia, parkinsonism in infancy, or progressive encephalopathy. These mutations indeed appear to reduce TH activity or influence expression of TH protein. Advances in molecular genetic studies provide a deeper understanding of the relationship between the alteration in TH activity and the pathology of catecholaminergic systems.
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PMID:Molecular genetics of tyrosine 3-monooxygenase and inherited diseases. 1610 53

Diacylglycerol kinase (DGK) phosphorylates the second messenger diacylglycerol (DAG) to yield phosphatidic acid, two neural signaling elements that function to modulate synaptic activity. Of the nine mammalian DGK isotypes known, DGK epsilon (DGKepsilon) shows specificity for arachidonoyldiacylglycerol (20:4-DAG) and selectively contributes to modulate brain signaling pathways linked to synaptic activity and epileptic seizure activity. In this study, we examined changes in gene transcription in a mouse kindling model of epileptogenesis using control DGKepsilon (+/+) and DGKepsilon-knockout (-/-) mice. Total RNA was isolated from the hippocampus and analyzed using RNA and DNA arrays. Significantly altered gene-expression levels were confirmed independently using Western immunoblot analysis. In agreement with our previous studies, a very few number of genes reached a significance of twofold or greater (either up- or down-regulated; p<0.05). Among the most significantly up-regulated genes in DGKepsilon (+/+) mice included those encoding the inducible prostaglandin synthase cyclooxygenase-2 (COX-2) and tyrosine hydroxylase (TH), also known as tyrosine 3-monooxygenase, the rate-limiting enzyme of catecholamine biosynthesis. Kindled DGKepsilon (-/-) animals exhibited no large increases in COX-2 or TH gene expression. These data, plus our previous findings that DGKepsilon (-/-) mice show higher resistance to electroconvulsive shock, suggest an interplay between and regulatory role for DGKepsilon, COX-2, and catecholamine signaling during kindling epileptogenesis.
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PMID:Epileptogenesis in diacylglycerol kinase epsilon deficiency up-regulates COX-2 and tyrosine hydroxylase in hippocampus. 1613 46

Melanocytes and neuroblasts share the property of transforming L-tyrosine through two distinct metabolic pathways leading to melanogenesis and catecholamine synthesis, respectively. While tyrosinase (TYR) activity has been shown to be expressed by neuroblastoma it remains to be established as to whether also glioblastomas cells are endowed with this property. We have addressed this issue using the human continuous glioblastoma cell line ADF. We demonstrated that these cells possess tyrosinase as well as L-tyrosine hydroxylase (TH) activity and synthesize melanosomes. Because the two pathways are potentially cyto-genotoxic due to production of quinones, semiquinones, and reactive oxygen species (ROS), we have also investigated the expression of the peroxisomal proliferators activated receptor alpha (PPARalpha) and nuclear factor-kB (NFkB) transcription factor as well the effect of L-tyrosine concentration on cell survival. We report that L-tyrosine down-regulates PPARalpha expression in ADF cells but not neuroblastoma and that this aminoacid and phenylthiourea (PTU) induces apoptosis in glioblastoma and neuroblastoma.
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PMID:Human glioblastoma ADF cells express tyrosinase, L-tyrosine hydroxylase and melanosomes and are sensitive to L-tyrosine and phenylthiourea. 1644 58

Tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2, TH) is the rate-limiting enzyme in the biosynthesis of catecholamine neurotransmitters, dopamine (DA), noradrenaline (NE), and adrenaline, in the neurons. The regulated activity of TH is thought to play a critical role in modulating the functional activity of catecholaminergic neuronal systems in the brain. It is well known that the catecholaminergic neuronal systems are associated with depression. Here we showed that TH, delivered by protein transduction domain (PTD), passed through the blood-brain barrier and entered the neurons. Systemic TH treatment improved the behavioral despair in the forced swim test (FST) and the tail suspension test (TST), the two models widely used to screen the potential anti-depressant efficacy. The results indicated a novel and potential therapeutic use of TH in the depression disorder.
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PMID:A novel therapeutic approach to depression via supplement with tyrosine hydroxylase. 1705 15

The most consistent neurochemical abnormality in Parkinson's disease is degeneration of dopaminergic neurons in the substantia nigra, leading to a reduction of striatal dopamine levels. The rate-limiting step in the biosynthesis of dopamine, noradrenalin, and adrenalin is catalyzed by tyrosine 3-monooxygenase (=tyrosine hydroxylase), which catalyzes the formation of L-DOPA. In earlier studies, we demonstrated that the novel synthetic sialic acid precursor N-propanoylmannosamine is a potent stimulator of axonal growth and promotes reestablishment of the perforant pathway from layer II of cortical neurons to the outer molecular layer of the dentate gyrus. Here we show that application of N-propanoylmannosamine leads to increased biosynthesis and secretion of dopamine. This increased biosynthesis of dopamine is due to decreased expression of O-linked N-acetylglucosamine on tyrosine 3-monooxygenase. Intracellular attachment of O-linked N-acetylglucosamine to serine and threonine residues hinders phosphorylation, thereby regulating the activity of the proteins concerned. We therefore propose a model in which the application of ManNProp leads to increased phosphorylation and activation of tyrosine 3-monooxygenase, which in turn leads to an increased synthesis of dopamine.
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PMID:N-propanoylmannosamine interferes with O-GlcNAc modification of the tyrosine 3-monooxygenase and stimulates dopamine secretion. 1789 94

Delta-like 1 (Dlk1), a member of the Delta/Notch protein family, is expressed in the mouse ventral midbrain (VM) as early as embryonic day 11.5 (E11.5) followed by exclusive expression in tyrosine 3-monooxygenase (TH) positive neurons from E12.5 onwards. To further elucidate the yet unknown function of Dlk1 in VM neuron development, we investigated the effect of soluble Dlk1 protein as well as the intrinsic Dlk1 function in the course of VM progenitor expansion and dopaminergic (DA) neuron differentiation in vitro. Dlk1 treatment during expansion increased DA progenitor proliferation and the proportion of NR4A2+ neurons expressing TH after differentiation, whereas Dlk1 treatment during the course of DA precursor differentiation did not alter TH+ neuron counts. In contrast, silencing of endogenously expressed Dlk1 prior to DA precursor differentiation partially prevented the expression of DA neuron markers, which was not accompanied with alteration of overall or local proliferation. Due to the latter finding in combination with the absence of Dlk1 negative DA neurons in differentiated cultures, we suggest that Dlk1 expression might have a permissive effect on DA neuron differentiation in vitro. The study presented here is the first publication identifying Dlk1 effects on ventral midbrain-derived DA precursor differentiation.
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PMID:Delta-like 1 participates in the specification of ventral midbrain progenitor derived dopaminergic neurons. 1798 27

Prostaglandin F2 alpha (PGF(2alpha)) brings about regression of the bovine corpus luteum (CL). This luteolytic property of PGF(2alpha) is used in beef and dairy cattle to synchronize estrus. A limitation of this protocol is insensitivity of the early CL to luteolytic actions of PGF(2alpha). The mechanisms underlying this differential luteal sensitivity are poorly understood. The developing CL has a maximum number of PGF(2alpha) receptors; therefore, differences in signaling events may be responsible for luteal insensitivity. Hence, differential gene expression at two developmental stages of CL, Day 4 (D-4) and D-10 after estrus, might account for differences in signal transduction pathways associated with luteal sensitivity. This possibility was examined in these studies. Microarray analysis (n = 3 cows per stage) identified 167 genes that were differentially expressed (P < 0.05). These were categorized into genes involved in protein biosynthesis and modification (18.5%), transcription regulation and DNA biosynthesis (18.5%), miscellaneous (17.0%), cell signaling (12.0%), steroidogenesis and metabolism (10.2%), extracellular matrix and cytoskeletal proteins (9.5%), unknown functions (6.0%), protein degradation (5.3%), and antioxidant property (3.0%). Real-time PCR confirmed the differential expression of nine selected genes, including tyrosine 3-monooxygenase/tryptophan 5-monooxygense activation protein zeta polypeptide (YWHAZ) and regulator of G protein signaling 2 24-kDa (RGS2), observed in microarray. Furthermore, the in vivo effect of exogenous PGF(2alpha) (n = 3 cows per stage) on selected genes that were found to be differentially expressed during this developmental transition was examined. PGF(2alpha) increased the expression of a guanine nucleotide-binding protein (G protein) beta polypeptide 1 (GNB1) in D-4 CL and calcium/calmodulin-dependent kinase kinase 2 beta (CAMKK2) in D-10 CL. Therefore, GNB1, CAMKK2, YWHAZ, and RGS2 are candidate genes that may have a significant role in acquisition of luteal sensitivity to PGF(2alpha). Additional evidence supporting the significance of the microarray data was obtained from the observation that the amount of CAMKK2 paralleled the differential mRNA expression observed for this gene when examined by microarray analysis and by real-time RT-PCR. Furthermore, the two types of luteal steroidogenic cells known to be targets for PGF(2alpha) actions were demonstrated to be a cellular source for CAMKK2.
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PMID:Differential gene expression in the bovine corpus luteum during transition from early phase to midphase and its potential role in acquisition of luteolytic sensitivity to prostaglandin F2 alpha. 1916 79

Tyrosine hydroxylase, an iron containing tetrahydrobiopterin dependent monooxygenase (tyrosine 3-monooxygenase; EC 1.14.16.2), catalyzes the rate-limiting step in which L: -dopa is formed from the substrate L-tyrosine. L-Dopa concentration and activity of L-tyrosine hydroxylase enzyme were measured in roots, stem, leaves, pods, and immature seeds of Mucuna pruriens. Immature seeds contained maximum L-dopa content and mature leaves possessed maximum catalytic activity of tyrosine hydroxylase. Tyrosine hydroxylase from leaf homogenate was characterized as a 55 kDa protein by SDS-PAGE and Western-blot analysis with monoclonal mouse IgG2a tyrosine hydroxylase antibody. The conditions for maximum tyrosine hydroxylase activity from the leaf extract were optimized with respect to temperature, pH, cofactor 6-MPH(4), and divalent metal ions. The tyrosine hydroxylase from leaf extract possessed a K (m) value of 808.63 microM for L-tyrosine at 37 degrees C and pH 6.0. The activity of the enzyme was slightly inhibited at 2,000 microM L-tyrosine. Higher concentrations of the cofactor 6-MPH(4), however, completely inhibited the synthesis of L-dopa. Tyrosine hydroxylase converted specific monophenols such as L-tyrosine (808.63 microM) and tyramine (K (m) 1.1 mM) to diphenols L-dopa and dopamine, respectively. Fe(II) activated the enzyme while higher concentration of other divalent metals reduced its activity. For the first time, tyrosine hydroxylase from M. pruriens is being reported in this study.
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PMID:Identification and optimization of tyrosine hydroxylase activity in Mucuna pruriens DC. var. utilis. 2030 Jul 71

Reverse transcription quantitative PCR (RT-qPCR) is a highly sensitive tool that can be used for accurate and reliable gene expression analysis; however, careful normalisation to a set of stably expressed endogenous reference genes is essential. Expression levels of many reference genes in RT-qPCR analyses can be extremely variable under different experimental conditions, producing potentially erroneous results (Bustin, 2002). This limitation can be overcome with a systematic evaluation of candidate reference genes to determine the most stable. In the present study eight candidate reference genes were evaluated in a bovine lymphoid (BL-3) cell culture system over seven different time points in response to three different Bovine Viral Diarrhoea Virus (BVDV) strains. Data were analysed using BestKeeper (Pfaffl et al., 2004), geNorm (Vandesompele et al., 2002), and NormFinder (Andersen et al., 2004) validation programs and results enable the candidate reference genes to be ranked from most to least stable. Quantification cycle (C(q)) variability was determined between samples, i.e. between treatment groups and time points, and variability was also observed between the three validation programs. The reference gene combination of beta-actin and hypoxanthine-guanine phosphoribosyl transferase (HPRT) was found to be the most stable in Norm Finder. BestKeeper and geNorm both demonstrated beta-microglobulin and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase (YWHAZ) as the most stable. The determination of a stable set of reference genes in the BL-3 cell culture system facilitates analysis of expression levels for appropriate genes of interest. This study further emphasises the need to accurately validate candidate reference genes before use in gene expression RT-qPCR studies.
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PMID:Validation of endogenous reference genes for RT-qPCR normalisation in bovine lymphoid cells (BL-3) infected with Bovine Viral Diarrhoea Virus (BVDV). 2058 Apr 38


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