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

---

Query: EC:1.14.16.2 (tyrosine hydroxylase)
14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effects of basic fibroblast growth factor (bFGF), which occurs in the adrenal medulla, on the survival, morphological phenotype, storage capacity for catecholamines and induction of the synthesizing enzymes tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) of cultured chromaffin cells from young postnatal rats. Basic FGF (40 ng/ml), like nerve growth factor (NGF; 40 ng/ml) prevented a drastic numerical decrease of chromaffin cells over a 4-day culture period, but, in contrast to NGF, did not induce neurite outgrowth, unless the cells were maintained for 7 days. Basic FGF was also more effective than NGF in maintaining the initial storage capacity for catecholamines, and even increased it under certain culture conditions (laminin instead of polyornithine, or 200 ng instead of 40 ng/ml). Basic FGF and NGF did not induce TH and PNMT activities beyond their initial levels, but partially prevented the reduction of TH activity seen after 4 days in culture. Based on the present data and the previously reported greater in vitro survival and transmitter stability of older chromaffin cells, which contain bFGF, and the relative instability of young postnatal chromaffin cells, which express no or very low levels of bFGF until 8 days postnatally, but respond to it, we hypothesize that bFGF is an important autocrine/paracrine maintenance factor for adult chromaffin cells.
...
PMID:Basic fibroblast growth factor promotes transmitter storage and synthesis in cultured chromaffin cells. 134 69

Basic fibroblast growth factor (bFGF) was injected with dissociated substantia nigral cells into the striatum of rats prepared by unilateral lesion of the nigrostriatal pathway with 6-hydroxydopamine. The transplanted cells with 5 and 50 ng bFGF reduced the apomorphine-induced rotations by 40 and 30%, respectively, while the decrement of rotations was only 15% in the grafted control without bFGF. Immunohistochemical staining with anti-tyrosine hydroxylase antibody showed that bFGF also tended to increase the number of grafted catecholaminergic neurons along the tracts. In the case of 50 ng bFGF treatment but not 0 or 5 ng bFGF treatment, however, severe gliosis was detected along the grafted region by staining of anti-glial fibrillary acidic protein antibody. These immunohistochemical studies suggested that high-dose bFGF induced extensive gliosis, which might affect the survival of the grafted neurons.
...
PMID:Basic fibroblast growth factor ameliorates rotational behavior of substantia nigral-transplanted rats with lesions of the dopaminergic nigrostriatal neurons. 143 31

We describe the isolation and characterization of an immortal cell line derived by infection of rat neural crest cells with a v-myc-containing replication-defective retrovirus. This clonal cell line, called NCM-1, contains a majority cell population with antigenic and morphologic properties that suggest it may represent a peripheral glial progenitor. In conditioned or in serum-free medium, these NGF receptor-positive cells differentiate to an elongated, bipolar morphology resembling that of primary Schwann cells. This morphologic differentiation is prevented by TGF-beta 1, which also acts as a mitogen for the cells. The NCM-1 line is also able to generate clonal derivatives which have extinguished expression of most or all glial markers. Once generated, such cells are stable and do not revert to the glial phenotype. At least some of these cells have acquired sympathoadrenal progenitor-like properties, as shown by their capacity to coexpress tyrosine hydroxylase (TH) and neurofilament (NF) in response to basic FGF and dexamethasone. These data imply that the NCM-1 line contains self-renewing cells with the potential to generate precursors in at least two of the sublineages that normally develop from the neural crest. This in turn suggests that the process of immortalization may preserve at least some of the developmental properties characteristic of multipotential neural crest cells. NCM-1 cells may prove useful for the study of neural crest cell lineage segregation, Schwann cell differentiation, and the mechanisms controlling the initial induction of TH and NF gene expression.
...
PMID:V-myc immortalization of early rat neural crest cells yields a clonal cell line which generates both glial and adrenergic progenitor cells. 167 38

Acidic fibroblast growth factor (aFGF) is a heparin-binding polypeptide that acts as a neurotrophic factor for certain central and peripheral neurons. Acidic FGF was injected stereotaxically into the striatum of young (2-month-old) and aging (12-month-old) C57BL/6 mice that were treated 1 week before with systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment (4 x 20 mg/kg, i.p. given 12 h apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and reduced dopamine (DA) concentration to 32% of the controls in young and 20% of the controls in aging mouse brain 5 weeks after administration. Although the DA concentration recovered to 43% of the controls in young mice following stereotaxic injection of aFGF 5 weeks after MPTP treatment, aging mice with such treatment did not show a significant recovery of DA concentration. Computerized image analysis of TH-IR fibers in the striatum also showed significant recovery in young mice treated with aFGF, while aging mice did not show a significant recovery. We conclude that treatment of MPTP-depleted young mice with aFGF results in partial recovery in the nigrostriatal DA system but such benefits decline with age.
...
PMID:MPTP-treated young mice but not aging mice show partial recovery of the nigrostriatal dopaminergic system by stereotaxic injection of acidic fibroblast growth factor (aFGF). 170 36

We sought to determine the source of the signal(s) that promotes expression of the catecholamine (CA) enzyme tyrosine hydroxylase (TH) in cultured neurons of embryonic rat cerebral cortex, a tissue which is not thought to contain CA cells in vivo. Cortical neurons were cultured with their non-neuronal constituents and 48 hr later immunostained for TH. Fibroblasts or glia had no effects, however, blood vessels increased the numbers of TH neurons nearly 4-fold. Coculture with either perinatal aorta, skeletal or cardiac muscle, clonal muscle cell lines 1440 (smooth) and L6 (skeletal), conditioned media from L6 cells, or a soluble extract of L6 cells increased the number of TH neurons up to 20-fold. The induction of TH by muscle extract was (1) dose dependent; (2) paralleled by a proportional increase in the steady-state levels of TH mRNA; (3) greatly reduced by the RNA synthesis inhibitor alpha-amanitin or the protein synthesis inhibitor cycloheximide; and (4) unassociated with change in the survival of neurons in culture. The response was not replicated by treatment with other established neurotrophic substances, including NGF, EGF, FGF, PDGF, neuroleukin, insulin, pyruvate, KCI, adenosine, or inosine. We conclude that muscle contains a potentially novel substance, muscle-derived differentiation factor (MDF) that promotes differentiation but not survival of neurons of cerebral cortex by de novo synthesis of TH mRNA and TH protein. Thus, neurons of the CNS, as in periphery, may undergo phenotypic interconversion in response to biologically derived molecules in their environment.
...
PMID:A muscle-derived factor(s) induces expression of a catecholamine phenotype in neurons of cultured rat cerebral cortex. 257 83

We describe features of the regulation of a neural-specific gene, SCG10, which is induced by nerve growth factor (NGF) during the neuronal differentiation of the rat pheochromocytoma cell line PC12. Induction of SCG10 mRNA occurs within 12-24 hr of exposure to NGF, is sustained in the continued presence of the neurotrophic factor, and involves a mechanism that is, at least in part, transcriptional. Unlike the rapid, transient transcriptional activations of genes such as c-fos, SCG10 induction requires ongoing protein synthesis, suggesting the participation of a de novo synthesized regulatory protein in mediating the effects of NGF on this gene. Although c-fos itself may play this role, its induction is clearly insufficient to cause an induction of SCG10. NGF, FGF, and, to a lesser extent, phorbol esters induced SCG10, whereas EGF and dibutyryl cAMP did not. In these characteristics, SCG10 induction appears to constitute a reliable molecular index of the transcription-dependent neuronal differentiation induced by NGF. Glucocorticoids, which inhibit NGF-induced neurite outgrowth from normal primary chromaffin cells, partially blocked SCG10 induction in PC12 cells. A reciprocal pattern of regulation by NGF and glucocorticoids was observed for tyrosine hydroxylase mRNA. These data suggest that environmental signals such as NGF may act on specific genes, both positively and negatively, to control the choice of alternative fates by developing neural crest cells.
...
PMID:The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable. 283 17

Substances found in the soluble extract of muscle can alter the differentiative fate of certain brain neurons in culture by triggering novel expression of the gene for the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) (Iacovitti et al., 1989; Iacovitt, 1991). In this study, we demonstrate that TH induction in cultured noncatecholamine neurons from the mouse striatum requires the cooperative interaction of at least two substances found in muscle. Purification studies, combined with biological assay, revealed that one necessary component is acidic fibroblast growth factor (aFGF), and the other, an unidentified molecule(s) of < 10 kDa molecular weight that activated aFGF. Thus, muscle-derived aFGF, if incubated in the presence but not the absence of the < 10 kDa fraction of muscle, induced a dose-dependent increase in the number of striatal neurons that novelly express TH. This expression was blocked by prior incubation and protein A precipitation of the factor with polyclonal antibodies to aFGF (1:200-1:1000). Similar to muscle-purified aFGF, commercial preparations of native bovine and human recombinant aFGF (0.1-100 ng/ml) were potent inducers of TH when coincubated with the < 10 kDa activator. In contrast, basic FGF produced little and FGF-7 no induction of TH. Unlike the unidentified activating agent in muscle, heparin (20-500 mU), a known activator of aFGF, did not potentiate the factor's TH-inducing activity. Nonetheless, heparatinase (100 mU) prevented TH induction by aFGF and its activator, indicating that binding of heparan sulfated proteoglycans is necessary for the effect.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Novel expression of the tyrosine hydroxylase gene requires both acidic fibroblast growth factor and an activator. 752 48

The phenotypically plastic neurons of the embryonic mouse striatum were used to explore mechanisms of catecholamine differentiation in culture. De novo transcription and translation of the CA biosynthetic enzyme, tyrosine hydroxylase (TH), was induced in striatal neurons exposed, simultaneously or sequentially, to the growth factor, acidic fibroblast growth factor (aFGF) and a catecholamine. Although dopamine was the most potent aFGF partner (ED50 = 4 microM), a number of substances, including dopamine (D1) receptor agonists, beta-adrenoceptor agonists, and dopamine uptake inhibitors also trigger TH induction when accompanied by aFGF. However, since none of the receptor antagonists nor transport blockers tested could inhibit dopamine's action, the mechanism remains obscure. Structure-activity analysis suggests that effective aFGF partners all contain an amine group separated from a catechol nucleus by two carbons. Thus, TH expression can be novelly induced by the synergistic interaction of aFGF, and to a lesser extent basic FGF, and a variety of CA-containing partner molecules. We speculate that a similar association between growth factor and transmitter may be required in development for the differentiation of a CA phenotype in brain neurons.
...
PMID:Synergy between growth factors and transmitters required for catecholamine differentiation in brain neurons. 754 1

Form-deprivation myopia (FDM) in the chick is a popular model for studying the postnatal regulation of ocular growth. Using this model, we have shown previously that dopamine and FGF-2 can counteract the effects of form-deprivation, thereby producing emmetropia. In the present study, we tested the hypothesis that the emmetropizing effects of flickering light and intraocular injections of FGF-2 in the chick are mediated by the activity of dopaminergic retinal amacrine cells. We have assessed the rate of dopamine synthesis in the retina by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA). We found that form-deprivation reduces the rate of dopamine synthesis in the light-adapted retina, and that the normal rate of dopamine synthesis in the light can be restored by stroboscopic illumination at frequencies around 10 Hz. By labeling cells immunocytochemically we have shown that the synthesis of c-fos, a putative transcriptional regulator of the tyrosine hydroxylase gene, is induced in dopaminergic amacrine cells by stroboscopic illumination at around 10 Hz. These observations are consistent with a critical role for dopaminergic amacrine cells in the regulation of ocular growth by intermittent illumination. We have found also that intraocular injections of FGF-2 cause emmetropization without altering levels of expression of c-fos, amounts of tyrosine hydroxylase, or rates of dopamine synthesis with respect to vehicle-injected controls. We conclude that FGF acts either in parallel to or downstream from the dopaminergic amacrine cells, rather than through them. We observed that intravitreal injection per se induces high levels of c-fos expression in both form-deprived and non-deprived retinas, and causes partial emmetropization in form-deprived eyes, while inhibiting dopamine synthesis in non-deprived retinas. It is likely, therefore, that injection stimulates the production and/or release of unknown factors whose diverse effects on ocular growth and dopamine metabolism are mediated by complex pathways. Taken together, our results are consistent with the view that the retinal circuitry that controls postnatal ocular growth in the chick involves multiple messengers and pathways.
...
PMID:Stimulation of dopaminergic amacrine cells by stroboscopic illumination or fibroblast growth factor (bFGF, FGF-2) injections: possible roles in prevention of form-deprivation myopia in the chick. 758 83

We investigated the effect of neurotrophic factors on dopamine (DA) cells in vitro. At concentrations of nanograms/c.c. basic fibroblast growth factor (bFGF) is a more potent DA-trophic agent than brain derived neurotrophic factor (BDNF) or epidermal growth factor (EGF) in fetal mid brain neurons. In these cells, bFGF produces a greater increase of DA levels and percentage of cells positive for tyrosine hydroxylase (TH+) than BDNF and EGF. Acidic fibroblast growth factor (aFGF) was not tested in fetal DA cells since aFGF requires heparin for its effect and fetal mid brain cultures do not grow well in the presence of a high concentration of heparin. We further investigated the effect of bFGF and aFGF, and two of their analogs, in catecholamine rich human neuroblastoma cells NB69. In these cells aFGF, at concentrations of picograms/c.c., increases DA levels, while its analogs, E118 and super short, have no effect. Acidic FGF also increases norepinephrine levels, the number of TH+ cells, and the percentage of TH+ with respect to the total number of nuclei. Basic fibroblast growth factor (bFGF) produced similar, but less potent effects. Acidic FGF was active only in the presence of heparin; the effect of bFGF was independent of heparin. FGFs are promising drugs for the treatment of PD, though further investigations with these compounds should be performed before their use in clinical trials.
...
PMID:Fibroblast growth factors: structure-activity on dopamine neurons in vitro. 760 86


1 2 3 4 Next >>

---