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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of the neurotrophic factor nerve growth factor (NGF) on the expression of the beta-amyloid gene has been studied in the clonal nerve cell line PC12. The neuronal differentiation of PC12 cells in the presence of NGF was accompanied by a shift in the ratio of beta-amyloid precursor protein (APP) transcripts. In particular there was reduced expression of the transcript coding for the longest precursor form (APP770) and a concomitant increase in the shortest (APP695) transcript following NGF treatment.
Brain Res Mol Brain Res 1991 Jul
PMID:Nerve growth factor-induced neuronal differentiation is accompanied by differential splicing of beta-amyloid precursor mRNAs in the PC12 cell line. 165 61

1. In situ hybridization histochemistry was used to localize nerve growth factor receptor (NGFR) mRNA in the adult rat basal forebrain. 2. In emulsion-dipped sections 35S-labeled RNA antisense probes produced a high density of silver grains over cells located in the medial septum, vertical and horizontal limbs of the diagonal band of Broca, and nucleus basalis. 3. This distribution of NGFR mRNA overlaps with the distribution of NGFR protein localized using immunocytochemical techniques. 4. No hybridization signal was detected when sections were hybridized with a 35S-labeled RNA sense (control) probe. 5. We suggest that NGFRs are synthesized in these basal forebrain nuclei and transported to terminal areas where NGF is thought to be bound and internalized, an initial step in the many actions of this neurotrophic factor.
Cell Mol Neurobiol 1990 Mar
PMID:Localization of nerve growth factor receptor mRNA in the rat basal forebrain with in situ hybridization histochemistry. 215 82

In vitro neural systems can be predictive for CNS neurotoxicity, except where xenobiotics primarily affect the blood-brain barrier. The wide range of systems now used in neurobiological studies is available for mechanistic neurotoxicological investigations although the choice of system is generally arbitrary. A more rational approach may now be justified. There are many culture systems available including neural cell lines, organotypic explant or reaggregation cultures, and primary monolayer cultures of individual neural cell types: neurons, astrocytes, and oligodendrocytes. Of these models much success has recently been achieved using the organotypic explant culture type. Similarly in our laboratories, using rat whole-brain reaggregate cultures, we have demonstrated good in vitro/in vivo correlations for the cholinergic neurotoxicant ethylcholine mustard aziridinium (ECMA) where specific cholinergic lesions are produced using low concentrations of ECMA (12.5 microM). Higher concentrations (25-50 microM) were more cytotoxic, as shown, for example, by nonspecific effects on cerebellar glutamatergic granule neurons. Treatment of reaggregates lesioned with the cholinotoxin with a neurotrophic factor, nerve growth factor (NGF), did not reverse the lesion but treatment of control cells with NGF (50 ng/ml) elevated both choline acetyltransferase (ChAT) activity and muscarinic receptor binding. The "lesioned" reaggregate culture system may thus be of future value in evaluating potential therapeutic agents that could reverse such lesions in the CNS. By supplementing the information gained in the reaggregate system with tests using primary monolayer cultures of neurons or astrocytes we can propose a stepwise screening system for potential neurotoxicants in vitro. In its simplest form this is (1) screen initially using tumor-derived neural cell line, (2) test selected compounds in whole-brain reaggregates, and (3) supplement information with primary monolayer cultures of individual neural cell types.
Mol Toxicol
PMID:Brain reaggregate cultures in neurotoxicological investigations: adaptational and neuroregenerative processes following lesions. 350 99

The hypothesis that peripheral, skeletal muscle tissue contains a trophic factor supporting central neurons has recently been investigated in vitro by supplementing the culture medium of spinal cord neurons with muscle extracts and fractions of extract. We extended these studies asking whether or not a trophic factor is present in peripheral nerves, the connecting link between muscle and central neurons via which factors may be translocated from muscle to neurons by the retrograde transport system. Lumbar, 8-day-old chick spinal cords were dissociated into single cells and then cultured in the presence of peripheral nerve extract. Cytosine arabinoside was added to inhibit proliferation of nonneuronal cells. In the presence of nerve extract, spinal cord neurons survived for more than a month, extended numerous neurites, and showed activity of choline acetyltransferase. In the absence of extract, neurons attached and survived for a few days but then died subsequently in less than 10 days. Neurite outgrowth did not occur in the absence of extract. Withdrawal of extract from the medium of established neuronal cultures caused progressive loss of both cells and neurites. Other tissues also contained neuron supporting activity but less than that found in nerve extract. These studies indicate that peripheral nerves contain relatively high levels of spinal cord neuron-directed trophic activity, suggesting translocation of neurotrophic factor from muscle to central target neurons. The neurotrophic factor has long-term (weeks) effects, whereas short-term (days) survival is factor independent.
Cell Mol Neurobiol 1984 Mar
PMID:Peripheral nerve extract promotes long-term survival and neurite outgrowth in cultured spinal cord neurons. 674 70

Hepatocyte growth factor (HGF), a natural ligand for the c-met protooncogene product, has mitogenic, motogenic and morphogenic activities for various cell types and functions as a organotrophic factor for regeneration of the liver, kidney and lung. We obtained evidence that HGF may function as a novel neurotrophic factor in the central nervous system. Northern blot analysis showed that 6 kb HGF mRNA and 9 kb c-Met/HGF receptor mRNA are expressed in various regions of the adult rat brain. In situ hybridization analysis revealed that intense hybridization signals for HGF mRNA were localized in cerebral cortex, hippocampus and amygdala. Consistently, specific localization of HGF protein in neurons of these regions was detected by immunohistochemical analysis and non-neuronal glial cells in cingulum, cerebellum, pons and medulla were also specifically stained. Specific intense hybridization signals for c-Met/HGF receptor mRNA were also widely distributed in the brain, including neurons of olfactory bulb, cerebral cortex, primary olfactory cortex, hippocampus and cerebellum. On the basis of the co-expression of HGF and c-Met/HGF receptor in hippocampal neurons, we found that HGF prolonged survival of embryonic hippocampal neurons in primary culture: HGF elicited maximal surviving effect at 0.5-1 ng/ml and the potency was comparable to that of nerve growth factor. More importantly, expression of both HGF and c-Met/HGF receptor mRNAs was markedly induced in response to cerebral ischemic injury. We propose that HGF functions as a neurotrophic factor in the central nervous system and that this neurotrophic function may have a role in the survival and reconstruction of specific neurons in response to cerebral injury.
Brain Res Mol Brain Res 1995 Sep
PMID:Localization and functional coupling of HGF and c-Met/HGF receptor in rat brain: implication as neurotrophic factor. 750 Aug 31

The detection of the glial cell-line derived neurotrophic factor (GDNF) mRNA by RT-PCR in dissociated cell culture of rat embryonic or post-natal brain allowed the amplification of a doublet. The major band corresponded to the expected size and the minor one to a shorter product. We cloned and sequenced the latter product, and thus identified a mRNA potentially encoding for an isoform of the initially described precursor protein involved in GDNF synthesis.
Brain Res Mol Brain Res 1995 Sep
PMID:GDNF: existence of a second transcript in the brain. 750 Aug 49

In situ hybridization was used to study the effect of IL-1 beta on acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) mRNA expression in rat brain. Intraventricular injection of recombinant human IL-1 beta did not affect hybridization to aFGF mRNA but did induce significant and widespread increases in hybridization to bFGF mRNA. IL-1 beta induced increases in bFGF mRNA were bilaterally distributed and appeared to correspond with the distribution of non-neuronal cells. Thus, hybridization was increased in regions of both gray and white matter (e.g., corpus callosum), the ependymal lining of the third ventricle, and the pia matter. In hippocampus of IL-1 beta injected rats, hybridization was markedly increased in the molecular layers but not significantly increased in the neuronal cell layers. Elevations in bFGF mRNA were transient, peaking at 8 h postinjection in most areas. To determine if IL-1 beta effects were independent of activation of the hypothalamo-pituitary-adrenal axis, and to compare the cellular localization of increases in bFGF mRNA expression induced by IL-1 beta and bFGF, the regulation of bFGF expression was also studied in organotypic hippocampal slice cultures. Treatment of cultures with either IL-1 beta or bFGF stimulated the same general distribution of increases in bFGF mRNA as seen after IL-1 beta treatment in vivo with an additional effect on immature neurons within the hilar side of stratum granulosum; hybridization of bFGF mRNA was not increased in association with the more mature neurons of stratum pyramidale or stratum granulosum. Colocalization of bFGF cRNA hybridization with immunostaining for glial fibrillary acidic protein demonstrated that increases in bFGF mRNA induced both by IL-1 beta in vivo and in vitro and by bFGF in vitro were largely associated with astroglial cells. These findings suggest that IL-1 beta induction of bFGF contributes to the coactivation of these substances following various forms of insult to the CNS and initiates a cascade of trophic interactions that regulates processes of glial proliferation, neurotrophic factor expression, and neuroprotection.
Brain Res Mol Brain Res 1994 Nov
PMID:Interleukin-1 beta increases basic fibroblast growth factor mRNA expression in adult rat brain and organotypic hippocampal cultures. 753 32

To elucidate the signal transduction mechanisms used by ligands that induce differentiation and the cessation of cell division, we utilized p13suc1-agarose, a reagent that binds p34cdc2/cdk2. By using this reagent, we identified a 78- to 90-kDa species in PC12 pheochromocytoma cells that is rapidly phosphorylated on tyrosine following treatment with the differentiation factors nerve growth factor (NGF) and fibroblast growth factor but not by the mitogens epidermal growth factor or insulin. This species, called SNT (suc-associated neurotrophic factor-induced tyrosine-phosphorylated target), was also phosphorylated on tyrosine in primary rat cortical neurons treated with the neurotrophic factors neurotrophin-3, brain-derived neurotrophic factor, and fibroblast growth factor but not in those treated with epidermal growth factor. In neuronal and fibroblast cells, where NGF can also act as a mitogen, SNT was tyrosine phosphorylated to a much greater extent during NGF-induced differentiation than during NGF-induced proliferation. SNT was phosphorylated in vitro on serine, threonine, and tyrosine in p13suc1-agarose precipitates from NGF-treated PC12 cells, indicating that this protein may be a substrate of kinase activities associated with p13suc1-p34cdc2/cdk2 complexes. In addition, SNT was associated predominantly with nuclear fractions following subcellular fractionation of NGF-treated PC12 cells. Finally, in PC12 cells, NGF-stimulated tyrosine phosphorylation of SNT was dependent on the levels of Trk tyrosine kinase activity and was constitutively induced by expression of pp60v-src. However, Ras was not required for constitutive SNT tyrosine phosphorylation, suggesting that this protein functions distally to Trk and pp60v-src but in a pathway parallel to that of Ras. SNT is the first identified specific target of differentiation factor-induced tyrosine kinase activity in neuronal cells.
Mol Cell Biol 1993 Apr
PMID:SNT, a differentiation-specific target of neurotrophic factor-induced tyrosine kinase activity in neurons and PC12 cells. 768 Nov 42

Alzheimer's disease and cognitive impairment in rats has been associated with an increase in the percentage of amyloid precursor protein (APP) containing the KPI domain. It has recently been reported that retinoic acid (RA) is capable of increasing the levels and altering the splicing ratio of APP in cultured SH-SY5Y cells. The effects of peripherally administered RA (64 or 640 micrograms/kg; i.p.; q.d.) on the abundance of APP, the ratio of the three major isoforms, and the relative abundance of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were determined by rtPCR in the hippocampus of aged rats. Corresponding changes in choline acetyltransferase (ChAT) activity were also measured. Vehicle (DMSO) treated rats exhibited a 2 x (P < 0.01) increase in total APP and an 8 x (P < 0.001) decrease in the cyclophilin transcript. In addition, DMSO increased the percentage of APP 695 from 89% in saline treated rats to 94%. Treatment of RA in DMSO decreased the accumulation of total APP relative to cyclophilin at both the low (6.4 x; P < 0.01) and high (8 x; P < 0.05) dosages when compared to DMSO treated rats. Furthermore, the level of APP-695 decreased to 82% with low dosage of RA and 75% at high dosage of the total APP transcripts. No significant change in either NGF, NT-3, or BDNF transcripts were observed following low or high dosage RA administration relative to cyclophilin RNA nor was a change in ChAT activity detected at either of the dosages tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1993 May
PMID:Altered levels and splicing of the amyloid precursor protein in the adult rat hippocampus after treatment with DMSO or retinoic acid. 768 85

Growth factors and their receptors function in the nervous system to induce proliferation and differentiation of neuronal precursor cells and to support survival of mature neurons. We have isolated a murine growth factor receptor tyrosine kinase using an anti-phosphotyrosine antibody screening procedure and studied the pattern of expression. The deduced amino acid sequence of the kinase has all the characteristics of a growth factor receptor and consists of a putative extracellular domain, a transmembrane domain, and a tyrosine kinase domain. Sequence comparison with known receptor tyrosine kinases indicated that the murine kinase is a mouse homolog of tyro3. tyro3 belongs to the Axl/Ufo growth factor receptor family. In the putative extracellular domain, there are two Ig-like domains and two fibronectin type III repeats which are conserved in other members of the Axl/Ufo family receptors. Northern blot hybridization analysis showed that tyro3 is expressed at high levels in the brain of adult mice, although considerable expression was also observed in the testis. In situ hybridization analysis revealed that high levels of tyro3 are expressed in the cerebral cortex, the lateral septum, the hippocampus, the olfactory bulb, and in the cerebellum. The highest levels of tyro3 expression in the brain are associated with neurons. The preferential expression of tyro3 in specific regions of the adult mouse brain suggests that tyro3 may function as a novel neurotrophic factor receptor.
Brain Res Mol Brain Res 1995 Feb
PMID:Isolation and expression analysis of tyro3, a murine growth factor receptor tyrosine kinase preferentially expressed in adult brain. 772 26


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