Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pheochromocytomas occur sporadically or in individuals affected by inherited syndromes including multiple endocrine neoplasia (MEN) type 2A and 2B, neurofibromatosis, and the von Hippel-Lindau syndrome (vHL). Medullary thyroid carcinomas (MTCs) also occur sporadically or as part of MEN 2A, MEN 2B, and familial MTC. Little is known of the molecular genetic background of these tumors. We have shown previously that activation of the N-ras, H-ras, and K-ras oncogenes does not occur in these tumors, but that deletions of the short arm of chromosome 1 are extremely common (> 60%) and may indicate loss of a suppressor gene in the chromosomal region 1p31-36. We have examined the structure and expression of N-myc, c-myc, L-myc, c-mos, nerve growth factor (beta-NGF), and the low affinity nerve growth factor receptor (LNGFR) in a series of pheochromocytomas and MTCs from patients with hereditary and sporadic diseases. Southern analysis, using radiolabeled DNA probes, revealed no evidence of amplification or rearrangement of these genes in any normal or tumor tissues except for loss of heterozygosity at the L-myc locus (1p32) in 9 pheochromocytomas from patients with MEN 2A or MEN 2B, in 5 of 11 non-MEN pheochromocytomas, and in 3 of 24 non-MEN MTCs. Gene expression at the RNA level was examined by Northern analysis or ribonuclease protection assay (RPA) using radiolabeled DNA or cRNA probes. C-myc transcripts were detectable at low levels in all tumors tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oncogene and growth factor expression in MEN 2 and related tumors. 136 25

The stabilities of different mRNA species were analyzed in a reticulocyte lysate system under protein-synthesizing conditions. In all cases examined the relative mRNA degradation by reticulocyte ribonucleases as well as by the interferon-modulated (2'-5') (A)n-dependent endonuclease correlated with the extent of (U)nA sequences within the 3' non-coding region. The experimental data presented indicate that according to their stabilities at least three major mRNA groups may be identified: (a) (U)nA-poor mRNAs (e.g. globin) are essentially stable and are only slightly degraded by the (2'-5')(A)n-dependent endonuclease; (b) mRNA species with intermediate (U)nA levels (e.g. Ig alpha and Ig mu heavy-chain mRNAs) are partially degraded by general ribonuclease activity and further degraded by the (2'-5')(A)n-dependent endonuclease and (c) (U)nA-rich mRNA species (such as c-myc and non-skeletal actin mRNAs) are inherently unstable and are extremely sensitive to degradation by general ribonuclease activity. A survey of mRNA nucleotide sequences demonstrated that without exception (U)nA-rich stretches appeared more frequently within the 3' non-coding region than in the coding or 5' non-coding regions. A comparison of 3' non-coding region sequences from 92 different mRNAs revealed that transiently expressed mRNAs, such as the interleukins, nerve growth factor, epidermal growth factor receptor, c-myc, c-fos, c-myb and several other oncogenes as well as interferons alpha, beta and gamma were exceptionally (U)nA-rich. It is postulated that differential mRNA stability may be partly determined by the primary nucleotide sequence and in particular by (U)nA sequences within the 3' non-coding region. This may represent a novel post-transcriptional strategy employed by the cell to selectively retain or destroy discrete mRNA species.
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PMID:Differential mRNA stability to reticulocyte ribonucleases correlates with 3' non-coding (U)nA sequences. 335

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

The Ba2+ currents and mRNA levels of four members of the rat brain family of alpha 1-subunit Ca2+ channel genes were examined and compared in the rat cell lines GH3 and PC-12 and in the mouse lines NIE-115 and AtT-20. The RNA was measured with ribonuclease protection assays using probes derived from rat brain (rb) Ca2+ channel cDNAs (rbA, rbB, rbC, and rbD), and the Ba2+ currents were studied by whole cell patch-clamp recording. L-, N-, P-, and T-type currents were discriminated by the voltage dependence and pharmacological properties of Ba2+ currents. All cell lines expressed all four rat brain Ca2+ channel genes, except GH3 cells, which lacked rbB. The functional diversity of Ba2+ currents, however, was quite different among the cell lines. GH3 cells showed evidence of L- and T-type currents, undifferentiated PC-12 cells of L-type currents, AtT-20 cells of L-, N-, and P-type currents, and undifferentiated NIE-115 cells of a T-type current that was partially blocked by both nifedipine and BAY K 8644. Dimethyl sulfoxide-differentiated NIE-115 cells also had an L-type current. Differentiation of NIE-115 cells caused an increase in the levels of rbB, rbC, and rbD RNAs. Differentiation by nerve growth factor caused an increase in levels of all four genes in PC-12. Our data give further support for the assignment of rbA, rbB, and rbC/rbD gene products as components of P-, N-, and L-type Ca2+ channels, respectively.
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PMID:Calcium channels in excitable cells: divergent genotypic and phenotypic expression of alpha 1-subunits. 752 Nov 26

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

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

The factors that determine the ability of some, but not all neurons, to sustain their axonal projections during aging remain largely unknown. Because sympathetic neurons remain responsive to nerve growth factor (NGF) in old age, it has been proposed that the selective decrease observed in the sympathetic innervation to some targets in aged rats may be the result of a deficit in target-derived NGF. In this study we utilized two different techniques to demonstrate decreased target innervation by sympathetic fibers in the aged rat pineal gland, which is an appropriate and relevant model for examining mechanisms of neuron-target interactions in aging. Tyrosine hydroxylase immunoreactive profiles were quantified in pineal glands of young and aged male Sprague-Dawley rats. The density of tyrosine hydroxylase-immunoreactive fibers was 30% lower in aged pineals, although the remaining fibers contained 20% more tyrosine hydroxylase-immunoreactivity. Othograde tracing of the pineal sympathetic innervation using biotinylated dextran revealed that average axon length, varicosity numbers, branch point numbers, and numbers of terminations were all decreased by approximately 50% in aged tissues, indicating possible functional deficits. These findings suggest that whole branches, along with their associated varicosities were lost in old age. A sensitive quantitative ribonuclease protection assay and a two-site ELISA assay were used to examine whether reduced NGF availability might correlate with sympathetic nerve atrophy. No significant differences were detected in either NGF mRNA or NGF protein levels when comparing young and aged pineal glands, suggesting that atrophy in aged sympathetic neurons is not causally related to reduced availability of NGF at the target. Our results indicate that mechanisms other than NGF expression need to be explored in order to explain the age-related axonal regression observed in this target.
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PMID:NGF expression in the aged rat pineal gland does not correlate with loss of sympathetic axonal branches and varicosities. 1067 35

These studies were performed to determine the developmental expression pattern of neurotrophic factor (NTF: nerve growth factor (betaNGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), neurotrophin-3 (NT-3) and NT-4 mRNA and NGF, NT-3 and NT-4 protein in the urinary bladder of the postnatal Wistar rat. It was hypothesized that NTFs may contribute to the development of the spinobulbospinal micturition reflex that represents the adult micturition pattern. Changes in NTF mRNA or protein expression in the urinary bladder at the time of development of the mature micturition reflex (postnatal days (P) 16-18) may suggest an involvement of target-derived NTFs in this maturation process. Developmental ages, prior to (P5, P10, P15) or following (P20, P30, adult P90) the development of the spinobulbospinal micturition reflex were selected and the urinary bladder was analyzed for levels of neurotrophic factor mRNA or protein. Results from ribonuclease protection assays demonstrated a similar developmental pattern among each neurotrophic factor examined. Neurotrophic factor mRNA levels increased by P10 and reach a maximum by P15. Subsequently, NTF mRNA levels declined to adult levels that were less than the earliest postnatal time examined (P5). NTF mRNA expression was significantly (p</=0.05-0.001) greater at P10, P15, P20 and P40 (NT-4 mRNA) compared to adult levels for each NTF examined except GDNF mRNA. In general, NGF, NT-3 and NT-4 urinary bladder protein levels in early postnatal development, as determined by ELISA, were similar when compared to the corresponding mRNA expression. Differences in the correlation between NT-3 and NT-4 mRNA and protein expression were demonstrated in the adult urinary bladder where significantly (p</=0. 001) greater levels of protein were revealed despite relatively low abundance of NT-3 and NT-4 mRNA. The developmental expression pattern (maximum expression at the second to third postnatal week) of NTFs in the urinary bladder is consistent with a potential role in the development of the spinobulbospinal reflex. Relatively high expression of NT-3 and NT-4 protein in the adult urinary bladder suggests a potential importance of these factors in the adult lower urinary tract.
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PMID:Developmental expression of urinary bladder neurotrophic factor mRNA and protein in the neonatal rat. 1067 71

Spinal cord injury and cyclophosphamide-induced cystitis dramatically alter lower urinary tract function and produce neurochemical, electrophysiological, and anatomical changes that may contribute to reorganization of the micturition reflex. Mechanisms underlying this neural plasticity may involve alterations in neurotrophic factors in the urinary bladder. These studies have determined neurotrophic factors in the urinary bladder that may contribute to reorganization of the micturition reflex following cystitis or spinal cord injury. A ribonuclease protection assay was used to measure changes in urinary bladder neurotrophic factor mRNA (betaNGF, BDNF, GDNF, CNTF, NT-3, and NT-4) following spinal cord injury (acute/chronic) or cyclophosphamide-induced cystitis (acute/chronic). The correlation between urinary bladder nerve growth factor mRNA and nerve growth factor protein expression was also determined. Each experimental paradigm resulted in significant (P </= 0.05-0.005) changes in urinary bladder neurotrophic factor mRNA, although the magnitude of the changes differed between paradigms. Urinary bladders from rats with acute spinal cord injury (4 days) exhibited the largest increase in neurotrophic factor mRNA levels (betaNGF, 21-fold increase; BDNF, 78-fold increase; GDNF, 11-fold increase; CNTF, 5.5-fold increase; NT-3, 10-fold increase; NT-4, 25-fold increase) relative to control urinary bladders. More modest but significant increases were demonstrated for urinary bladders from rats with chronic (4-6 weeks) spinal cord injury. Significant increases in urinary bladder neurotrophic factor mRNA levels of comparable magnitude were demonstrated following either acute or chronic cyclophosphamide-induced cystitis. Increased abundance of urinary bladder nerve growth factor mRNA was not always associated with increased total urinary bladder nerve growth factor. Total urinary bladder nerve growth factor decreased following acute or chronic cystitis despite increased abundance of nerve growth factor mRNA. Urinary bladder nerve growth factor mRNA correlates with protein measures 5-6 weeks following spinal cord injury but not earlier. The 5- to 6-week time point coincided with the reemergence of the spinal bladder-to-bladder reflex mechanisms following spinal cord injury. Discrepancies between two measures (mRNA and protein) may reflect retrograde axonal transport of nerve growth factor to the dorsal root ganglia (L6-S1). Retrogradely transported NGF may play a role in altered lower urinary tract function following spinal cord injury or cyclophosphamide-induced cystitis.
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PMID:Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction. 1068 93

The present studies were undertaken to characterize the regional and temporal patterns of neurotrophin messenger RNA and protein levels for beta-nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the developing CNS. We have examined the levels of these neurotrophin messenger RNAs with ribonuclease protection assays and corresponding protein levels with enzyme-linked immunosorbent assays in the developing Long-Evans rat hippocampus, neocortex and cerebellum on postnatal days 1, 7, 14, 21, and 92. In addition, immunohistochemistry was used to localize the neurotrophins in these developing brain regions. Results indicated that in neocortex and hippocampus, messenger RNA for both nerve growth factor and brain-derived neurotrophic factor increased in an age-dependent manner, reaching a plateau by postnatal day 14. In the neocortex, nerve growth factor and brain-derived neurotrophic factor protein levels both peaked at postnatal day 14. In hippocampus, nerve growth factor protein peaked at postnatal day 7 while brain-derived neurotrophic factor peaked at postnatal day 14. In cerebellum, nerve growth factor messenger RNA levels were flat, while nerve growth factor protein peaked at postnatal day 7. Brain-derived neurotrophic factor messenger RNA increased in an age-dependent manner while the pattern for its protein levels was mixed. Neurotrophin-3 messeger RNA levels increased in an age-dependent manner in hippocampus, peaked at postnatal day14 in cerebellum, and no changes occurred in neocortex. Neurotrophin-3 protein was at its peak at postnatal day 1 and thereafter decreased at other postnatal days in all three brain regions. Results of neurotrophin immunohistochemistry often paralleled and complemented enzyme-linked immunosorbent assay data, demonstrating specific cell groups containing neurotrophin proteins in these regions. Within each region, patterns with regard to messenger RNA and respective protein levels for each neurotrophin were unique. No consistent relationship between patterns of neurotrophin messenger RNAs and their cognate proteins was observed between regions. The different regional patterns for neurotrophin messengerRNA and protein levels in each brain region indicate that messenger RNA studies of neurotrophin messenger RNA must be augmented by protein determination to fully characterize spatial and temporal neurotrophin distribution.
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PMID:Differential patterns of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNA and protein levels in developing regions of rat brain. 1127 92


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