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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recently cloned neurotrophic factor, termed glial cell line-derived neurotrophic factor (GDNF), has been reported to exhibit selective neurotrophic properties on ventral mesencephalon dopaminergic neurons, which degenerate in patients with Parkinson's disease. In the present study, we used reverse transcriptase followed by polymerase chain reaction (PCR) and in situ hybridization to study the expression of GDNF messenger RNA (mRNA) in the adult rat and human central nervous system (CNS). GDNF transcripts were identified using PCR in all regions of the rat CNS analyzed including striatum, hippocampus, cortex, cerebellum, and spinal cord. Interestingly, the rat hippocampal formation contained two transcripts, i.e., a larger form in addition to the amplified GDNF cDNA found in all other areas analyzed. GDNF PCR products also were observed in human striatum, hippocampus, cortex, and spinal cord, but not cerebellum, and both the striatum and hippocampal formation contained two GDNF transcripts. Finally, GDNF transcripts were detected in a rat Schwann cell line previously shown to secrete a factor that exerts a neurotrophic effect on dopaminergic neurons. In situ hybridization experiments using a cRNA probe hybridized to adult rat brain sections demonstrated no positive GDNF mRNA signal. However, intense GDNF mRNA hybridization signal was found to be associated with dorsal root ganglia in Postnatal Day 1 rats. These findings provide evidence that GDNF is detectable using PCR in a number of nervous system structures and, in some areas, GDNF is expressed in more than one form.
...
PMID:Expression of GDNF mRNA in rat and human nervous tissue. 803 59

Glia cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, has been implicated in the survival, morphological and functional differentiation of midbrain dopaminergic neurons and motoneurons in vitro and in vivo. The factor may thus have utility in the treatment of various human neurodegenerative disorders. Mechanisms regulating expression of GDNF in normal and diseased brain as a possible means to increase the local availability of GDNF are only beginning to be explored. We have established and employed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to study and compare levels of expression of GDNF mRNA in several cell types and to investigate its regulation. GDNF expression was clearly evident in primary cultured astrocytes, the glioma B49 and C6 cell, but less pronounced in the Schwannoma RN22 cell lines. Little or no signal could be observed in neuroblastoma cell lines (IMR32, LAN-1) or the pheochromocytoma cell line PC12, emphasizing the glial character of this factor. Using the C6 cell line we found that fibroblast growth factor-2 (FGF-2; bFGF) can increase GDNF mRNA levels, whereas FGF-1, platelet-derived growth factor (PDGF), and vasoactive intestinal polypeptide (VIP) are apparently ineffective. Several other factors (forskolin, kainic acid, triiodothyronine dexamethasone, GDNF, TGF-beta 1, and interleukin-6) appear to have slightly negative effects on GDNF mRNA levels at the concentrations tested. To further explore the relationship between FGF-2 and GDNF, we also addressed the question whether GDNF, like FGF-2, may have an effect on C6 cell proliferation. We conclude that (1) glial and glial tumor cells, rather than neuronal cell lines, express GDNF, (2) that FGF-2 has a prominent inductive effect on GDNF expression and (3) that GDNF stimulates C6 cell proliferation. Finally, these data suggest that neurotrophic actions of FGF-2 in mixed glial-neuronal cell cultures might be mediated in part by GDNF.
...
PMID:GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells. 888 50

Trefoil polypeptides are expressed mainly in the amphibian skin and the gastrointestinal tract of mammals, usually coexpressed with mucin-glycoproteins. Recently, the trefoil polypeptides were shown to be expressed also in different areas of the human and murine brain. To investigate the expression and possible functions of ITF in rat pheochromocytoma (PC12) cells were employed. PC12 cells show a low basal expression of this polypeptide as determined by reverse transcriptase-polymerase chain reaction. After treatment with the synthetic glucocorticoid dexamethasone, the second messenger cyclic adenosine monophosphate and the neurotrophic factor nerve growth factor the expression of the trefoil polypeptide ITF was increased as shown by reverse transcriptase-polymerase chain reaction and by immunocytochemistry. Since these various stimuli can directly can directly alter the expression level of this peptide we conclude that the presented results may from the basis for further investigations of possible functions of this novel gut-brain polypeptide in neurons using PC12 cells.
...
PMID:Expression of the trefoil polypeptide ITF in PC12 cells. 923 42

Application of neurotrophic factors (NFs) to the cut stump of motor nerves of neonatal rats confers neuroprotection from trauma-induced neuronal death. To test whether motoneurons are capable of responding to endogenously produced NFs, facial motoneurons were genetically modified in vivo to express several NFs and then tested for their response to peripheral nerve damage. Replication-defective adenoviral vectors [Adv. Rous sarcoma virus (RSV)-nf] representing three families of NFs were constructed that carried genes for brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor. Media from cultured cells transduced with Adv. RSV-nf contained NFs that supported the survival of cultured chick sensory neurons in the same manner as recombinant NF standards. When Adv.RSV-nf or an adenoviral vector containing the beta-galactosidase gene (Adv.RSV-beta-gal) were injected into the facial muscles of neonatal rats the vectors were retrogradely transported to the facial nucleus where the NFs or beta-gal were expressed. A fraction (approximately 10%) of the neurons were transduced as demonstrated by reverse transcriptase-PCR, histochemistry, and immunocytochemistry. In the case of Adv.RSV-BDNF, Adv.RSV-CNTF, and Adv.RSV-GDNF, a significant portion of the facial nucleus neurons was protected, 16.5, 18.2, and 53.3%, respectively, from death after axotomy, showing that neurons are capable of transporting the Adv. RSV-nf, expressing the recombinant NF genes, and responding to the NFs. In the case of Adv.RSV-GDNF, a greater number of facial nucleus motoneurons survived than were transduced, indicating that neighboring untransduced neurons were protected by the GDNF expressed by the transduced neurons by a paracrine mechanism.
...
PMID:Targeted transduction of CNS neurons with adenoviral vectors carrying neurotrophic factor genes confers neuroprotection that exceeds the transduced population. 925 62

During mammalian cortical development, neuronal precursors proliferate within ventricular regions then migrate to their target destinations in the cortical plate, where they organize into layers. In the rat, most cortical neuronal migration occurs during the final week of gestation (Bayer et al, 1991; Jacobson, 1991). At this time (E15-E21), reverse transcriptase-polymerase chain reaction demonstrated that cortical homogenates contain mRNA encoding brain derived neurotrophic factor (BDNF) and the catalytic form of its high-affinity receptor, TrkB. Immunocytochemistry and in situ hybridization of sections revealed that the catalytic TrkB receptors predominantly localize to regions containing migratory cells. Many TrkB+ cells exhibited the classic morphology of migrating neurons, suggesting that TrkB ligands play a role in cortical neuronal migration. We analysed whether TrkB ligands influence the motility of embryonic cortical cells (from E15-E21) using a quantitative in vitro chemotaxis assay. High-affinity TrkB ligands (BDNF and NT4/5) stimulated chemotaxis (directed migration) of embryonic neurons at concentrations ranging from 1 to 100 ng/ml. NT-3, a low-affinity TrkB ligand, only stimulated significant migration at high concentrations (> or =100 ng/ml). Peak migration to BDNF was observed at gestational day 18 (E18). BDNF-induced chemotaxis was blocked by either tyrosine kinase inhibitor, K252a, or the Ca2+-chelator, BAPTA-AM, suggesting that BDNF-induces motility via autophosphorylation of TrkB receptor proteins and involves Ca2+-dependent mechanisms. BDNF-stimulation of increased cytosolic Ca2+ was confirmed with optical recordings of E18 cortical cells loaded with Ca2+ indicator dye. Thus, signal transduction through the TrkB receptor complex directs neuronal migration, suggesting that, in vivo, BDNF exerts chemotropic effects that are critical to morphogenesis of the cortex.
...
PMID:Neurotrophins stimulate chemotaxis of embryonic cortical neurons. 951 61

Over the past few years, it has been reported that physical and psychological stress elevate plasma interleukin-6 (IL-6), and that neural cells can produce IL-6 and have receptors for IL-6 (IL-6R). However, it is unknown whether IL-6 plays a role in regulating the functions of neural cells in response to stress. We demonstrated recently, using the reverse transcriptase-polymerase chain reaction (RT-PCR), that the levels of mRNAs for IL-6 and IL-6R in the rat brain are changed by restraint stress for four hours. In the present study, we investigated the expression of mRNAs for IL-6 and the IL-6R in the rat hypothalamus and midbrain during restraint stress. After rats had been restrained for 10, 30, 60, 120 or 240 min, the hypothalamus and midbrain were removed immediately and levels of IL-6 mRNA and of IL-6R mRNA in these regions were determined by RT-PCR. The expression of mRNAs for IL-6 and IL-6R in both regions was reduced after short-term (30-60 min) restraint stress and tended to return toward the control level after 120 min restraint stress. After long-term (240 min) restraint stress, the level of IL-6 mRNA was significantly increased in the midbrain, while the level of IL-6R mRNA was significantly reduced in both regions. These findings suggest that the need for IL-6 might decline after short-term restraint stress and, moreover, that the synthesis and secretion of IL-6 might be enhanced and IL-6 might be needed as a neurotrophic factor in the midbrain after long-term stress.
...
PMID:The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R) in the rat hypothalamus and midbrain during restraint stress. 965 Nov 20

N-methyl-D-aspartate (NMDA) receptor subunit expression changes during development and following injury in several brain regions. These changes may be mediated by neurotrophic factors, such as brain derived neurotrophic factor (BDNF). Exposure of cultured cortical neurons to BDNF (100 ng/ml) for 24 h produced a significant decrease in the NMDA-induced whole-cell currents sensitive to the NR2B subunit selective NMDA receptor antagonist, CP-101,606, suggesting a relative decrease in NR2B subunit expression. There was a significant increase in NR2A by Western blot analysis. Consistent with the electrophysiology and Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) amplification revealed that BDNF caused a significant increase in relative NR2A subunit expression, a significant decrease in relative NR2B subunit expression and no change in relative NR2C subunit expression. These results suggest that BDNF enhances NMDA receptor maturation, warranting further study of the mechanism of BDNF effects on NMDA receptor subunit expression and the role these effects play in development and neuronal injury.
...
PMID:Brain derived neurotrophic factor induction of N-methyl-D-aspartate receptor subunit NR2A expression in cultured rat cortical neurons. 973 98

Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neurotrophic effects on motor neurons as well as mesencephalic dopaminergic neurons. Because GDNF promotes survival of motor neurons in vivo and in vitro and rescues motor neurons from naturally occurring cell death, the potential use of GDNF for treatment of motor neuron diseases has been a major focus of recent research. The expression of GDNF in humans, however, has not been fully examined. In the present study, we examined the expression of GDNF in adult human muscle by Northern blot, reverse transcriptase polymerase chain reaction (RT-PCR), and immunohistochemical analyses to address physiological roles of GDNF in humans. Northern blot analysis demonstrated high expression of GDNF mRNA in human skeletal muscle when compared to that of mouse. Intense GDNF immunoreactivity was observed in the vicinity of plasma membranes of skeletal muscle, particularly at neuromuscular junctions. GDNF immunoreactivity was also observed within the axons and surrounding Schwann cells of peripheral nerves. However, RT-PCR detected expression of GDNF mRNA only in skeletal muscle, and not within the anterior horn cells of human spinal cord. These results suggest that GDNF is produced by skeletal muscle and taken up at the nerve terminals for retrograde transport by axons. Thus, GDNF in human skeletal muscle may be involved in promoting motor neuron survival as a target-derived neurotrophic factor.
...
PMID:Prominent expression of glial cell line-derived neurotrophic factor in human skeletal muscle. 985 1

To understand the mechanism underlying cognitive deficits in AIDS patients, we examined the influence of gp41 peptides on the expression and the secretion of Alzheimer's amyloid precursor protein (APP) in human astroglial cell line T98G. Western blotting analyses demonstrated that treatment of glial cells with a putative immunosuppressive domain (aa 583-599) of gp41 remarkably downregulated the interleukin 1beta- (IL-1beta) induced elevation of the secreted form of APP (sAPP alpha) containing Kunitz-type protease inhibitor (KPI) domain without significant changes of the expression pattern of APP mRNAs as revealed by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Recombinant gp41 protein encoding for ectodomain, including aa 583-599 residues, also elicited a similar dose-dependent inhibitory effect, whereas the control peptides resulted in little change. The molecular mechanism underlying this gp41-mediated reduction of sAPP alpha secretion appears not to be owing to the difference in the function of extracellular proteases based on the finding of similar proteolytic activities responsible for APP metabolism in vitro present in the conditioned media from the cultures treated with or without gp41 peptide. However, the known PKC inhibitors such as H-7 or staurosporine, partially inhibited the elevation of sAPP alpha secretion in response to protein kinase C (PKC) agonist phorbol 12,13-dibutyrate (PdBu) as well as to IL-1beta, mimicking the immunosuppressive gp41 peptide. These observations implicate that part of the neurodegenerative cascade in AIDS brains may involve the inhibitory effect of gp41 on secretion of sAPP alpha, a potent glial neurotrophic factor, through impaired PKC response.
...
PMID:Effect of HIV-1 gp41 peptides on secretion of beta-amyloid precursor protein in human astroglial cell line, T98G. 1052 58

Glial cell line-derived neurotrophic factor (GDNF), a sequence-related factor of the transforming growth factor-beta family, has been identified as a potent neurotrophic factor for a variety of neuronal cell populations. At present, it is still unknown whether human gliomas in vivo are also capable of producing GDNF. We studied the expression of GDNF in 14 human glioblastomas, 1 gliosarcoma and 5 astrocytomas. Using an enzyme-linked immunosorbent assay, the amount of GDNF was quantified in human gliomas and compared to GDNF-expression in C6 glioma cells, mouse fibroblasts and normal human and rat brain. Mean concentration of GDNF in gliomas was 937 +/- 140 pg GDNF/g tissue (n = 20). C6 cells revealed the highest expression levels of 2,837 +/- 813 pg/g, whereas mouse 3T3 fibroblasts showed no detectable GDNF protein. Mean GDNF tissue levels in normal human and rat brain were significantly lower. Using reverse transcriptase-polymerase chain reaction, GDNF mRNA was detected in human gliomas and in rat C6 cells. Immunohistochemistry revealed strong GDNF- and GDNF receptor-alpha 1-expressing tumor cells in human glioma tissue. These results show that glial tumors, even in the most dedifferentiated form of glioblastoma, express GDNF at concentrations up to five times higher compared to normal human brain. This overexpression of GDNF may be of biological relevance for proliferation of glial tumors in humans.
...
PMID:Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GFR-alpha 1) are strongly expressed in human gliomas. 1067 19


1 2 3 Next >>

---