Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present work we determined, by Northern blotting, ribonuclease assay and in situ hybridization, the level of multiple trkB and trkC transcripts at different times after ibotenic acid-induced neuronal injury in the rat hippocampus. All the transcripts (7.0-7.5, 2.4 and 1.8 kb) encoding the truncated TrkB receptor are coordinately up-regulated following neurotoxic injury, with a time-course similar to that observed for the glial fibrillary acidic protein mRNA, a molecular marker of reactive astrocytes. The highest level of induction was observed for the 2.4 kb mRNA level. The 1.8 kb mRNA, whose relative level is higher in astroglial cultures compared to normal brain tissue, is detectable only in the gliotic hippocampus. The 9 kb trkB mRNA, which encodes the full-length TrkB receptor, rapidly decreases with a time-course similar to that previously observed for other neuronal markers. In situ hybridization studies show that the increased mRNA level per cell is a major determinant in the up-regulation of truncated trkB expression. A decrease of truncated and full-length trkC mRNA was observed in the neuron-depleted astroglia-enriched hippocampus, suggesting that this mRNA is mainly localized in the neuronal layers and that no induction of its expression occurs in reactive astrocytes.
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PMID:Neurotoxic injury in rat hippocampus differentially affects multiple trkB and trkC transcripts. 750 Dec 31

By northern blot analysis and ribonuclease protection assay, we observed the presence of a high level of trkB mRNA in primary brain cultures devoid of neuronal cells and highly enriched in glial fibrillary acidic protein-positive astroglial cells prepared from newborn rat cerebral hemispheres, cerebral cortex, hippocampus, and striatum. In primary astroglial cultures, the more abundant trkB transcripts code for the truncated receptor without tyrosine kinase activity; probes specific for the full-length trkB mRNA did not detect any signal in northern blot analysis. By the sensitive ribonuclease protection assay, we could show the presence of trkC mRNA in cultured astrocytes, whereas no trkA mRNA was detected. We confirmed the presence of relatively high levels of nerve growth factor and neurotrophin-3 mRNA, and very low basal level of brain-derived neurotrophic factor mRNA. Moreover, we demonstrated that another member of the neurotrophin family, neurotrophin-4, is also expressed in cultured astroglial cells. In view of the fact that many functional receptors for conventional neurotransmitters or neuropeptides present on astroglial cells may act via the adenylate cyclase system, we studied also the effect of agents able to increase the intracellular cyclic AMP concentration. A sharp increase in the trkB mRNA level was observed after treatment of primary astroglial cultures with dibutyryl cyclic AMP, 8-bromo-cyclic AMP, or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine. On the contrary, trkC mRNA levels were unaffected by treatment with cyclic AMP-elevating agents. All the neurotrophin mRNAs examined, except neutrophin-4, were increased by 3-isobutyl-1-methylxanthine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of neurotrophins and their receptors in primary astroglial cultures: induction by cyclic AMP-elevating agents. 751 99

Degenerate primers directed against conserved regions of the trk and trkB amino acid sequences were used in the polymerase chain reaction to isolate a 455 bp fragment from embryonic day 3 chicken cDNA encoding the trkC. This fragment was subsequently used to synthesize an anti-sense trkC cRNA probe which was used in a RNase protection assay of total RNA from chicken embryos. trkC mRNA was found in the E2 embryo with increasing levels later in development. In the E9 embryo highest levels were found in brain and spinal cord with intermediate levels in eye, heart, gut and muscle. Low levels were found in kidney, liver, skin and yolk sac. Using the 455 bp trkC fragment as a probe in RNA blot analyses of poly A+ RNA, a major transcript of 6.3 kb and two minor transcripts of 3 kb and 10 kb were found. In situ hybridization was performed on embryos taken at three stages of development (embryonic day 3, 9 and 19), using a 48-mer antisense oligonucleotide probe for chicken trkC. Within the sensory nervous system trkC mRNA expression at all ages was confined to the ventrolateral neurons of the spinal sensory and trigeminal ganglia as well as distal ganglia associated with the VIIth, IXth and Xth cranial nerves. Labelling for trkC mRNA was also observed within the developing CNS at E3 and the ganglion of Remak at E19. A barely detectable level of expression was observed in the sympathetic chain and no labelling was evident in the proximal ganglia of the cranial nerves. These results suggest that neurons have a very early capacity to respond to neurotrophin-3 which continues throughout embryonic development. The early expression of trkC mRNA also support the growing evidence suggesting a role for neurotrophins in neuronal differentiation.
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PMID:Molecular cloning and cellular localization of trkC in the chicken embryo. 826 14

The adult rat dorsal root ganglion (DRG) produces mRNA for the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and contains large populations of neurons responsive to these factors. We report that following a focal crush injury of the sciatic nerve, NGF mRNA expression increases threefold and BDNF mRNA two-fold, in the ipsilateral L4 and L5 DRGs. The mRNAs encoding the cognate neurotrophin receptors, p75NGFR, trkA, and trkB were expressed in the DRG throughout the post-injury time course, suggesting that DRG neurons remain responsive to both NGF and BDNF. p75NGFR mRNA levels became transiently depressed in the DRG during the first several days after the lesion but returned to normal within 1 week. trkB mRNA was expressed in the normal sciatic nerve and levels were not altered by nerve crush. RNase protection assays detected both full-length and truncated trkB transcripts in the DRG, but only truncated trkB mRNA, lacking the tyrosine kinase domain, was detected in the sciatic nerve. Likewise, trkA transcripts were not detected by RNase protection in normal sciatic nerve or in a segment of nerve distal to the crush site. These results are consistent with a model in which regenerating sensory neurons are supported by neurotrophic factors synthesized within the DRG.
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PMID:Expression of mRNA for neurotrophic factors and their receptors in the rat dorsal root ganglion and sciatic nerve following nerve injury. 827 14

The presence of the neurotrophin, nerve growth factor, brain derived neurotrophic factor, neurotrophin-3 and neurotrophin-4 (NGF, BDNF, NT-3 and NT-4) and their receptors of the tyrosine kinase family (trkA, trkB and trkC) have been investigated in the choroid plexus and dura mater of the adult rat by ribonuclease protection assay. The choroid plexus contained high levels of mRNAs for NGF and NT-4, and low levels of NT-3 and BDNF mRNA; and high levels of trkB mRNA, and undetectable levels of trkA and trkC mRNA. In the dura mater there were high levels of NT-3 and NGF, and low levels of BDNF and NT-4 mRNAs; and high levels of trkC mRNA, and relatively high amount of trkB mRNA, while levels of trkA mRNA was undetectable. The present analysis revealed a different distribution of neurotrophins and their related receptors in the choroid plexus and dura mater.
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PMID:Expression of mRNAs for neurotrophins and their receptors in the rat choroid plexus and dura mater. 858 Apr 26

Previous studies have analyzed the expression of different members of the neurotrophin family and their trk receptors in glial cultures composed mainly or exclusively of type-1 astrocytes, whereas only partial data have been published on other cultured glial types. In this article we compare the mRNA levels for neurotrophins (NGF, BDNF, NT-3, NT-4) and their high-affinity receptors (trkA, trkB, trkC) in cultures enriched in specific glial types, such as microglia, type-1 astroglia, and cells of the O/2A lineage (type-2 astroglia and oligodendroglia). Relatively high levels of NGF mRNA (comparable to those observed in adult rat cerebral cortex) are present in all types of cultured glial cells, except for a low level of expression in cultures enriched in microglial cells. In contrast, BDNF mRNA is undetectable in all cultures examined. NT-3 and NT-4 mRNA molecules, at a level equal to that observed in adult rat cerebral cortex, are easily detected in type-1 astrocyte cultures, whereas their hybridization signals are undetectable in cells of the O/2A lineage and in microglial cultures. The analysis of neurotrophin receptor mRNAs confirms the absence of trkA mRNA, the presence of relatively high levels of trkB mRNA (70-100% of cerebral cortex values), and low levels of trkC mRNA (10-18% of cerebral cortex values) in both cultured astroglial and oligodendroglial cells. Only very low levels of trkB and trkC mRNAs are observed in microglial cultures. Although cultured glial cells express mainly mRNAs encoding for the truncated form of trkB and trkC, a low level of mRNA encoding for the full-length catalytic form of these receptors is detected by the sensitive ribonuclease protection assay.
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PMID:Neurotrophins and their trk receptors in cultured cells of the glial lineage and in white matter of the central nervous system. 886 Feb 35

The neurotrophins brain-derived neurotrophic factor (BDNF) and NT-4/5 exert their trophic effects on the nervous system via signaling through trkB receptors. These receptors occur as splice variants of the trkB gene that encodes a full-length receptor containing the signal transducing tyrosine kinase domain as well as truncated forms lacking this domain. Because the importance of the trkB isoforms for development and maturation of the nervous system is unknown, we have examined the expression of trkB receptor isoforms during development of the rat forebrain using 1) a sensitive ribonuclease protection assay to distinguish full-length and truncated trkB transcripts, 2) western blot analysis to characterize developmental changes in trkB proteins, and 3) immunohistochemistry to determine the cellular localization of trkB receptors. In the rat forebrain, adult mRNA levels for full-length trkB are reached by birth, whereas truncated trkB message does not peak until postnatal days 10-15. Western blot analysis indicates that full-length trkB protein is the major form during early development, whereas truncated trkB protein predominates in all forebrain regions of late postnatal and adult rats. These data also suggest that the glycosylation state of these receptors changes during postnatal maturation. TrkB immunoreactivity is present predominately within neurons, where it is localized to axons, cell soma, and dendrites. Strong dendritic immunostaining is particularly evident in certain neuronal populations, such as pyramidal neurons in the hippocampus and in layer V of the neocortex. The dendritic localization of trkB receptors supports the hypothesis that dendrites, as well as axons, are important sites for neurotrophin actions in the central nervous system.
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PMID:Developmental and mature expression of full-length and truncated TrkB receptors in the rat forebrain. 889 44

The expression of neurotrophin and neurotrophin receptor mRNAs in human granulocytes and bone marrow cells was examined using ribonuclease protection assay and reverse transcription-polymerase chain reaction. The granulocytes expressed mRNA coding for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-4 (NT-4), but not neurotrophin-3 (NT-3). Moreover, the inflammatory mediator leukotriene B4 (LTB4) up-regulated the expression of NT-4 mRNA in granulocytes, but did not affect the expression of other neurotrophin mRNAs. Granulocytes generally lacked expression of mRNA coding for neurotrophin receptors. In contrast, human bone marrow cells consistently expressed mRNA for trkB (the BDNF and NT-4 receptor) and displayed variable expression of mRNA coding for trkA (the tyrosine kinase NGF receptor) and LNGFR (the low-affinity NGF receptor), whereas mRNA for trkC (the NT-3 receptor) was not expressed. Contrary to granulocytes, normal bone marrow cells generally expressed only low levels of mRNA encoding BDNF and NT-4. Expression of mRNA encoding NGF and NT-3 was not detected. However, significantly increased expression of BDNF mRNA was observed when bone marrow cells from patients with chronic myeloproliferative disorders (MPD) were analyzed. The results suggest that neurotrophins may act as granulocyte-derived effector molecules and that human bone marrow cells may be targets for these compounds, in particular BDNF and NT-4.
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PMID:Expression of mRNA encoding neurotrophins and neurotrophin receptors in human granulocytes and bone marrow cells--enhanced neurotrophin-4 expression induced by LTB4. 971 63

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, regulate synaptic functions in the hippocampus of the adult rodent. In previous studies, in situ hybridization methods have been used to evaluate regional differences in BDNF and trkB mRNA expression levels in hippocampal subregions. However, these studies have failed to reach consensus regarding the regional differences in the mRNA expression levels. In the present study, we quantitated mRNA expression levels using two different methods, ribonuclease protection assays and a quantitative reverse-transcription polymerase chain reaction technique, in four hippocampal subregions: the entorhinal cortex, dentate gyrus (DG), CA3 and CA1. These two methods yielded the same results. We found that BDNF and trkB mRNA expression levels did not covary in the four subregions. BDNF and full length trkB (trkB FL) mRNA in the entorhinal cortex and the DG show contrasting expression patterns. The expression level of BDNF mRNA was highest in the DG among the hippocampal subregions and low in the entorhinal cortex and the CA1, whereas the trkB FL mRNA expression level was highest in the entorhinal cortex, low in the DG and lowest in the CA3. These results suggest regional differences in BDNF/TrkB signaling for maintenance and modifiability of neuronal connections in the hippocampal formation.
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PMID:Highest trkB mRNA expression in the entorhinal cortex among hippocampal subregions in the adult rat: contrasting pattern with BDNF mRNA expression. 981 29

Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-alpha) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expressed in the thyroid tissue. Therefore, it is unlikely that these factors serve a direct local autocrine or paracrine function in thyroid cell types, and a target-derived mode of action on neurons innervating the thyroid tissue is suggested. An opposite result has been found for the neurotrophic factor GDNF: thyroid tissue showed a high level of transcripts for the GDNF receptor subunits (GDNFR-alpha and Ret), while GDNF mRNA was undetectable. The in situ hybridization analysis of GDNFR-alpha and ret mRNA revealed an interesting difference in the cell distribution of these transcripts: ret mRNA is selectively expressed in a subpopulation of cells scattered in the follicular epithelium and in the interfollicular spaces, while GDNFR-alpha expression is more homogeneous and widespread, including the more abundant cell type of the thyroid gland: the follicular cell. Double-labeling in situ hybridization/immunocytochemistry experiments, with a specific marker (calcitonin), showed that parafollicular cells express ret but not GDNFR-alpha. This differential distribution of the GDNF receptor components (GDNFR-alpha and ret) may reflect a peculiar biological role in intercellular communication in the thyroid gland.
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PMID:Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue. 1002 66


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