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)

We have studied the effects of basic fibroblast growth factor on rat embryonic mesencephalic neurons in vitro. Basic fibroblast growth factor promotes the survival of dopaminergic neurons in vitro, the effect increasing with dose and reaching a maximum at 10 ng/ml. In the absence of basic fibroblast growth factor the number of tyrosine hydroxylase-stained (tyrosine hydroxylase positive) neurons declines to almost zero within 14 days, whereas in the presence of basic fibroblast growth factor numbers remain almost constant from three to 28 days in vitro. This effect of basic fibroblast growth factor is abolished by preventing non-neuronal cells from appearing in the cultures, apart from a basic fibroblast growth factor-mediated increase in the numbers of tyrosine hydroxylase-positive cells during the first two days in vitro. The presence or absence of non-neuronal cells also influences dopaminergic neuronal morphology, the neurons having more, longer, and more varicose processes in the absence of astrocytes. Survival of dopaminergic neurons in vitro in the absence of basic fibroblast growth factor is very dependent on plating cell density, but in the presence of basic fibroblast growth factor this dependency vanishes. It is also possible to make survival independent of plating density by growing the cultures on inverted coverslips, which have the effect of concentrating secreted molecules in the thin layer of medium between coverslip and dish. Our conclusions from these experiments on plating density are that astrocytes probably constitutively secrete a small amount of a trophic factor which promotes survival of dopaminergic neurons, and that the rate of production of this factor is greatly increased by basic fibroblast growth factor. If basic fibroblast growth factor is withdrawn from cultures after two or seven days the dopaminergic neurons soon die. However, if basic fibroblast growth factor is withdrawn after 14 days, after the period of naturally occurring cell death of these neurons, there is no increase in dopaminergic neuronal death compared to controls in which basic fibroblast growth factor treatment is maintained. If basic fibroblast growth factor is used to improve the survival of dopaminergic neurons grafted in vivo, it should therefore be sufficient to treat the grafts for 14 days.
 ...
PMID:Basic fibroblast growth factor promotes the survival of embryonic ventral mesencephalic dopaminergic neurons--I. Effects in vitro. 790 40

Brain-derived neurotrophic factor, basic fibroblast growth factor and des(1-3)-insulin-like growth factor-1, a brain specific form of insulin-like growth factor-1, were analysed, in the rat, for their influence on survival, morphological growth, and transmitter-specific differentiation of dopaminergic neurons in vitro. Brain-derived neurotrophic factor, des-insulin-like growth factor-1, and basic fibroblast growth factor were found to differentially regulate development of dopaminergic cells. Brain-derived neurotrophic factor stimulated survival, the formation of primary neurites and dopamine uptake activity. des-Insulin-like growth factor-1 was most effective in promoting survival, stimulated dopamine uptake less effectively than brain-derived neurotrophic factor and did not alter the morphology of dopaminergic cells. Basic fibroblast growth factor produced comparatively mild increases in survival and dopamine uptake, and slightly reduced neurite growth of the cells. None of the factors stimulated the expression of the tyrosine hydroxylase gene. These findings suggest that (i) effective growth factors may stimulate different, but partially overlapping, molecular pathways during developmental differentiation, (ii) none of the factors stimulates dopaminergic cell differentiation comparable to the pronounced trophic action of nerve growth factor on peripheral sympathetic or basal forebrain cholinergic neurons, and (iii) localization and effects of none of the factors are compatible with a role as target-derived survival-regulating neurotrophic factor.
 ...
PMID:The nature of the trophic action of brain-derived neurotrophic factor, des(1-3)-insulin-like growth factor-1, and basic fibroblast growth factor on mesencephalic dopaminergic neurons developing in culture. 809 10

Studies have suggested that the restorative effects of adrenal medullary chromaffin cell grafts in animal models of Parkinson's disease may be related to trophic factors contained within the chromaffin cells. Basic fibroblast growth factor (bFGF) is present in chromaffin cells and has been shown to exert trophic effects on dopaminergic neurons in vitro. Basic FGF was stereotaxically injected into the striatum of young (2-month-old) and aging (12-month-old) C57BL/6 mice which had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1 week earlier. MPTP treatment reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and striatal dopamine (DA) concentration in both the young and older mice 5 weeks later. Computerized image analysis of striatal DA fibers in young mice treated with bFGF showed significant recovery of DA fibers up to 600 microns from the injection site 5 weeks after MPTP administration. Striatal DA fibers in older mice treated with bFGF showed significant recovery only up to 300 microns from the injection site, and the degree of recovery was very limited compared with young mice. HPLC analysis of DA concentration revealed that striatal DA in young mice recovered significantly when treated with bFGF, but no significant recovery was observed in older mice. It is concluded that bFGF enhances the recovery of striatal DA systems from MPTP toxicity both in young and in older mice, but that such benefits are very limited in older mice.
 ...
PMID:Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging. 810 13

Basic fibroblast growth factor (bFGF) promotes the survival and growth of dopaminergic neurons. We have investigated the effect of treating fetal ventral mesencephalon with bFGF or nerve growth factor (NGF) on the subsequent survival and function of grafted dopaminergic neurons implanted into the striatum of rats with a unilateral 6-hydroxydopamine lesion. Animals implanted with fetal ventral mesencephalon mixed with bFGF, but not with NGF, displayed more rapid compensation in motor behavior up to 9 weeks after graft implantation. bFGF, but not NGF, produced an increase in the number of tyrosine hydroxylase (TH)-positive neurons, a larger graft volume, and longer neurite outgrowth in comparison to control grafts. bFGF also increased the number of glial fibrillary acidic protein (GFAP)-positive astrocytes within the grafts. The increased number of GFAP-positive astrocytes induced by bFGF correlated with the increase in the number of TR-positive neurons, with graft volume and with neurite outgrowth. These findings support the use of bFGF to promote the functional integration of fetal ventral mesencephalon grafts into the denervated host brain and and suggest that its action may be indirectly mediated through glial cells.
 ...
PMID:Altered motor function and graft survival produced by basic fibroblast growth factor in rats with 6-OHDA lesions and fetal ventral mesencephalic grafts are associated with glial proliferation. 865 24

Basic fibroblast growth factor (bFGF) prevents damage to the nigrostriatal system in rodents. We now report the effects of bFGF administered by intraventricular infusion to adult common marmosets (Callithrix jacchus) previously rendered parkinsonian by the administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Infusion commenced 10 weeks after MPTP treatment and the animals received bFGF in low (1.8 micrograms/l), medium (18 micrograms/l), or high (180 micrograms/l) doses over a 28-day period. At weekly intervals, automated activity measurements, behavioral disability scoring, and videotape analyses were made. There was no improvement in the motor deficits exhibited by MPTP-treated common marmosets receiving bFGF infusion compared to vehicle-treated controls. Three of five high dose animals showed neurological impairment prior to the end of the study. No significant differences were found between control and bFGF-infused MPTP-treated common marmosets with respect to nigral tyrosine hydroxylase immunoreactive cell counts and striatal [3H]mazindol binding. All high dose animals showed hydrocephalus which was also observed in four other animals receiving bFGF. Histological examination revealed proliferation of the choroid plexus and ependyma which was most marked in the high dose animals. Adverse effects, in the form of hydrocephalus and neurological deterioration, were presumably secondary to an ependymal and choroid plexus reaction induced by bFGF.
 ...
PMID:Intraventricular infusion of basic fibroblast growth factor (bFGF) in the MPTP-treated common marmoset. 880 47

Our previous studies indicate that, in the noncatecholamine (non-CA) neurons of the striatum, expression of the gene for the CA biosynthetic enzyme tyrosine hydroxylase (TH) can be initiated by the synergistic interaction of acidic fibroblast growth factor (aFGF) and a second partner molecule. In this study, we sought to determine whether the activators of protein kinase C (PKC) signaling pathways, either alone or in conjunction with various growth factors, is sufficient to induce TH in striatal neurons. We found that when the active beta from of 4 beta-12-O-tetradecanoylphorbol 13-acetate (TPA), but not the inactive alpha analogue, was incubated in the presence of aFGF, basic FGF, or brain-derived neurotrophic factor, TH expression was initiated. Activation of the PKC pathways alone (in the absence of growth factors) did not mimic these effects, suggesting that multiple pathway activation is required for novel TH expression. Although other specific activators of PKC were effective growth factor partners, TPA was the most potent with an ED50 of 0.008 muM. Conversely, inhibitors of protein kinases, such as H7, H8, or H89, prevented the expression of TH by aFGF and TPA. Because pretreatment with protein (cycloheximide) or RNA synthesis (amanitin and actinomycin D) inhibitors eliminated the inductive effect of aFGF and TPA, we conclude that de novo transcription and translation are necessary for the expression of TH after convergence of both PKC and growth factor pathways.
 ...
PMID:Protein kinase C activators work in synergy with specific growth factors to initiate tyrosine hydroxylase expression in striatal neurons in culture. 900 41

The goal of this study was to examine the responsiveness of an immortalized catecholaminergic neuronal line, 2N27, to various growth factors and identify those which promote catecholaminergic expression. 2N27 is a newly established neural cell line derived from fetal rat mesencephalic tissue and, thus, contains tyrosine hydroxylase (TH), a reliable marker for catecholaminergic neurons. Using TH activity as a biochemical index, we examined the responsiveness to both recognized trophic factors (NGF, TGF-beta and basic- and acidic-FGF) as well as novel, glia-derived factors present in conditioned media from several glial sources. The glial cells included MACH, a normal cell line derived from aged mouse cerebral hemispheres NBCC, normal glia derived from newborn mouse cerebral hemispheres; and C-6 glioma cells, 2B clone, passage 72, predominately astrocytes. Cells were cultured in the presence of added factors from 0 to 3 days in vitro (DIV) and were harvested on day 4. We found that 2N27 neural cells responded differentially to growth factors. No change was observed in TH activity in response to NGF, TH activity even decreased in response to b-FGF ad TGF-beta addition to the culture medium. However, a dose dependent increase in TH activity was observed following treatment with a-FGF and the increase to a-FGF was associated to an increase in cell proliferation as compared to TH increase by cAMP associated to differentiation. However, the 2N27 cells responded with a marked increase in TH when cultured in the glial cell conditioned media. We conclude that immortal cells require a variety of microenvironmental signals to maintain their phenotype.
 ...
PMID:Catecholaminergic expression in 2N27 immortal neural cell line is enhanced by glial-derived factors. 905 60

Crest-derived glomus cells of the carotid body (CB) are O(2)-sensitive chemoreceptors, which resemble sympathoadrenal (SA) chromaffin cells. In this study, we tested whether perinatal rat glomus cells are sensitive to basic fibroblast growth factor (bFGF) in vitro and whether their sensitivity is regulated by oxygen. In chemically defined medium, bFGF (1-100 ng/ml) caused a significant, dose-dependent increase in the number of surviving tyrosine hydroxylase-positive (TH+) glomus cells in embryonic (E17-E19) CB cultures, following a 48-hr exposure. Though basic FGF (10 ng/ml) appeared mitogenic for these cells, based on stimulation of bromodeoxyuridine (BrdU) uptake, it supported survival of only approximately 60% of the initial TH+ population, suggesting that significant cell death was occurring. This apparent cell loss in E17 cultures could be largely prevented by combined treatment with bFGF and low oxygen (6% O(2)). In contrast, in early postnatal (P1) cultures, glomus cell number was relatively unchanged over 48 hr under control conditions or in presence of mitogenic activity from either bFGF or low oxygen. However, combined treatment with both bFGF and low oxygen stimulated proliferation of P1 glomus cells such that by 48 hr the TH+ population had increased to approximately 1.5x the initial density. Basic FGF (10 ng/ ml) also stimulated neurite outgrowth and neurofilament expression in E18-E19, but not P1-P3, glomus cells. In contrast to bFGF, treatment with nerve growth factor was ineffective. Taken together, these results suggest that bFGF and low oxygen are mitogens for perinatal CB chromaffin cells and interact cooperatively as survival factors. It is plausible that these mechanisms may operate to regulate chemoreceptor cell density, during the animal's transition from in utero (hypoxic) to ex utero (normoxic)life.
 ...
PMID:Role of basic FGF and oxygen in control of proliferation, survival, and neuronal differentiation in carotid body chromaffin cells. 913 30

Basic fibroblast growth factor (FGF-2) mediates numerous important physiological processes, including differentiation and survival of dopaminergic neurons. FGF-2 was found to trigger elevation of tyrosine hydroxylase (TH) gene expression in PC12 cells that was sustained for 1-8 days. FGF-2 induced chloramphenicol acetyltransferase (CAT) reporter activity under control of the TH promoter, indicating that the induction is transcriptionally mediated. The transcriptional activation of TH by FGF-2 was examined using various deletions and point mutations of the 5' flanking region controlling CAT reporter activity. In contrast to the reported mechanisms of transcriptional regulation of TH expression by NGF and phorbol esters, the AP-1 site at -205/-199 was not required for the activation by FGF-2. A construct containing only 60 nucleotides of the promoter was still inducible by FGF-2. However, a construct with a point mutation in the CRE/CaRE was not responsive to induction by FGF-2. These findings indicate that the CRE/CaRE, but not the AP-1, element is required for induction by FGF-2 and point to differences between NGF and FGF-2 in the regulation of TH gene expression.
 ...
PMID:Requirement for cAMP/calcium response element but not AP-1 site in fibroblast growth factor-2-elicited activation of tyrosine hydroxylase gene expression in PC12 cells. 938 81

We have shown previously that the synergistic interaction of acidic fibroblast growth factor (aFGF) and a coactivator (dopamine, protein kinase A, or protein kinase C activator) will induce the novel expression of tyrosine hydroxylase (TH) in neurons of the developing striatum. In this study we sought to determine whether, concomitant with TH expression, there were unique changes in transcription factors binding the AP-1 regulatory element on the TH gene. Indeed, we found a significant recruitment of proteins into TH-AP-1 complexes as well as a shift from low- to high-affinity binding. Supershift experiments further revealed dramatic changes in the proteins comprising the AP-1 complexes, including recruitment of the transcriptional activators c-Fos, a novel Fos protein, Fos-B, and Jun-D. Concomitantly, there was a decrease in repressor-type factors ATF-2 and CREM-1. aFGF appeared to play a central but insufficient role, requiring the further participation of at least one of the coactivating substances. Experiments examining the signal transduction pathway involved in mediating these nuclear events demonstrated that the presence of only an FGF (1, 2, 4, 9) competent to induce TH caused the phosphorylation of mitogen-activated protein kinase (MAPK). Moreover, the treatment of cells with MEK/ERK inhibitors (apigenin or PD98059) eliminated TH expression and the associated AP-1 changes, suggesting that MAPK was a critical mediator of these events. We conclude that, during transdifferentiation, signals may be transmitted via MAPK to the TH-AP-1 site to increase activators and reduce repressors, helping to shift the balance in favor of TH gene expression at this and possibly other important regulatory sites on the gene.
 ...
PMID:Regulation of tyrosine hydroxylase gene expression during transdifferentiation of striatal neurons: changes in transcription factors binding the AP-1 site. 976 63


<< Previous 1 2 3 4 Next >>