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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the genes encoding the beta/A4 amyloid protein precursor (APP) and microtubule-associated protein tau was studied in an embryonal carcinoma cell line (P19) that differentiates in vitro into cholinergic neurons after treatment with retinoic acid. Expression of APP increased 34- (mRNA) and 50-fold (protein) during neuronal differentiation; APP-695 accounted for most of this increase. These remarkable increases in APP expression coincided with a proliferation of neuronal processes and with an increase in content of tau mRNA. Moreover, subsequent decreases in the levels of APP and tau mRNA coincided with the onset of the degeneration of the neuronal processes. Immunocytochemical staining suggested that greater than 85% of the P19-derived neurons are cholinergic and that APP is present in the neuronal processes and cell bodies. These results suggest that APP may play an important role in construction of neuronal networks and neuronal differentiation and also indicate that this embryonal carcinoma cell line provides an ideal model system to investigate biological functions of APP and the roles of APP and tau protein in development of Alzheimer's disease in cholinergic neurons.
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PMID:Increased expression of beta-amyloid protein precursor and microtubule-associated protein tau during the differentiation of murine embryonal carcinoma cells. 156 Feb 39

The direct effects of the neurotransmitter serotonin on the catecholaminergic enzyme, tyrosine hydroxylase and the microtubule-associated tau protein were studied in a human neuroblastoma cell line. Undifferentiated LAN-5 cells, cultured in serum supplemented basal medium, or cells induced to differentiate by 6 day exposure to 10 uM retinoic acid were treated for 48 hr with 50 nM and 50 uM serotonin. In undifferentiated cells, serotonin treatment (50 uM) decreased both tyrosine hydroxylase activity and a 50 kD cytoplasmic fraction tau protein while 50 nM serotonin treatment caused this 50 kD protein to increase in the cytoplasmic fraction but decrease in the membrane fraction. While basal tyrosine hydroxylase activity increased in differentiated vs. undifferentiated cells, serotonin treatment had no effect on the enzyme or tau in differentiated LAN-5. This study shows serotonin to have direct effects on the biochemistry and cytoskeleton of undifferentiated cultured human neuroblastoma.
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PMID:Effects of serotonin on tyrosine hydroxylase and tau protein in a human neuroblastoma cell line. 168 52

The presence of the trivalent metallic cations, aluminum and boron, in the culture medium of differentiated human LAN-5 neuroblastoma cells results in increased amounts of specific isomers of microtubule-associated tau proteins. The cells were differentiated to a neuronal phenotype by the addition of retinoic acid. Six-day exposures of the differentiated cells to a 1-mM dose of aluminum or boron yielded increases in tau protein immunoreactivity to the monoclonal antibodies Tau-1 and Alz-50. Significant increases in immunoreactivity were seen at treatment levels of aluminum down to 100 microM. The increases in tau proteins were independent from increases in levels of total cell protein. Control cultures treated with the divalent cations zinc and iron showed no increases in levels of tau proteins.
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PMID:Effects of aluminum on tau proteins in human neuroblastoma cells. 195 63

Neuronal hybrid ND 7/23 cells, which display sensorylike properties, develop neurites when cultured in the presence of either dibutyryl cyclic AMP plus nerve growth factor (DBcAMP + NGF) or retinoic acid or a phorbol ester derivative, although they express only trace amounts of the microtubule-associated tau proteins and low levels of microtubule-associated protein 2c (MAP2c). Nondifferentiated ND cells transfected with tau cDNAs did not develop neurites, whereas very short cell processes were formed in MAP2c-transfected cells. tau and MAP2 antibodies labeled microtubule bundles displayed in a ring array underneath the surface of the transfected cells and short microtubules starting from the cell center. After differentiation in the presence of DBcAMP + NGF, the same bundle organization was observed in the transfected cells. In addition, tau and MAP2 antibodies stained a short section of the formed neurites. These data demonstrate that the expression of tau protein is not sufficient to induce neurite extension and that other proteins induced by morphogens are more important to initiate morphological differentiation of this cell line.
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PMID:Tau and microtubule-associated protein 2c transfection and neurite outgrowth in ND 7/23 cells. 786 Nov 33

We studied the expression of the NO synthase isoforms in an in vitro model of neural development using RT-PCR, Western blot and immunohistochemistry. Murine PCC7-Mz1 cells (Jostock et al., Eur. J. Cell Biol. 76, 63-76, 1998) differentiate in the presence of all-trans retinoic acid and dibutyryl cAMP along the neural pathway into neuron-like, fibroblast-like and astroglia-like cells. Undifferentiated cells showed immunofluorescent staining for neuronal-type NOS I and endothelial-type NOS III. This expression pattern was retained in those cells differentiating into neurofilament- and tau protein-positive neuronal cells. Thymocyte alloantigen (Thy1.2/CD 90.2)-positive fibroblasts, appearing around day 3, and glial fibrillary acidic protein (GFAP)-positive astroglial cells, appearing after day 6 of differentiation, stained negative for any NOS isoform. Starting at day 6 of differentiation, expression of inducible-type NOS II could be stimulated with cytokines in a subset of cells, which may represent activated astrocytes. NOS II was always undetectable in non-induced cultures. These data indicate that the ability of stem cells to express NOS I and NOS III is only retained when the cells differentiate along the neuronal lineage, while a small subpopulation of cells acquires the ability to express NOS II in response to cytokines.
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PMID:Analysis of NO synthase expression in neuronal, astroglial and fibroblast-like derivatives differentiating from PCC7-Mz1 embryonic carcinoma cells. 1009 36

Tau proteins are encoded by a single gene which is regulated by a unique promoter. The proximal 196 base pairs of the tau 5' flanking region confers tau protein with neuronal specific expression and nerve growth factor inducibility. We tested tau promoter activity in neuronally differentiated embryonal carcinoma cells, the P19 mouse blastoderm cell line. In these experiments, we examined the temporal expression pattern of the tau promoter and compared it to other viral and cellular promoters. Tau promoter activity increases significantly with differentiation, specifically during neurite initiation. In addition, tau promoter activity in neuronally differentiated P19 cells was significantly greater than all five of the other neuronal or non neuronal promoters tested. All other promoters displayed low levels of promoter activity throughout retinoic acid induced neuronal differentiation of P19 cells. Taken together, our results suggest that the tau promoter is a good choice for ectopic expression of exogenous genes in P19 cells, which serves as a differentiating neuronal model system.
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PMID:Tau promoter activity in neuronally differentiated P19 cells. 1093 17

Early onset generalized dystonia is a severe form of primary dystonia linked to a mutation of the DYT1(TOR1A) gene on chromosome 9q34. DYT1 gene codifies for human torsinA, an AAA+ ATPase associated with the membranes of endoplasmic reticulum (ER) and the synaptic vesicles and proposed to be involved in trafficking of tubular-vesicular membrane through neuronal processes. In this study, the presence and the intracellular distribution of torsinA protein in SH-SY5Y neuroblastoma cells were evaluated by immunofluorescence and Western blot analysis following differentiation with retinoic acid and BDNF. Protein expression was then inhibited by transient antisense transfection and the possible effect on neurite outgrowth was observed. In SH-SY5Y cells torsinA, with an apparent MW of 38 kDa, is endogenously present and distributed, with a punctate pattern, in the cytosol and along the neurites. The protein showed high intensity of immunoreactivity in the neurite varicosities and was partially co-localized with vesicles markers. Terminally differentiated cells showed an increase of protein expression. Oligonucleotide antisense treatment induced a significant response to differentiating stimuli, lead to sprouting of longer neurites and increase in growth cone areas. A relationship between torsinA and tau protein, which is involved in axon elongation and establishment of neuronal polarity, was demonstrated by co-immunoprecipitation experiments. These findings suggest that torsinA, throughout the interaction with microtubule associated proteins, may contribute to control neurite outgrowth and could be involved in maintaining cell polarity.
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PMID:TorsinA negatively controls neurite outgrowth of SH-SY5Y human neuronal cell line. 1515 63

The paired helical filaments of highly phosphorylated tau protein are the main components of neurofibrillary tangles (NFT) in Alzheimer's disease (AD). Protein kinases including glycogen synthase kinase 3 beta (GSK3beta), cyclin-dependent kinase 5 (Cdk5), and c-Jun N-terminal kinase (JNK) have been implicated in NFT formation making the use of selective kinase inhibitors an attractive treatment possibility in AD. When sequentially treated with retinoic acid (RA) and brain-derived neurotrophic factor (BDNF), the human neuroblastoma SH-SY5Y differentiates to neuron-like cells. We found that coincident with morphologically evident neurite outgrowth, both the content and phosphorylation state of tau increased in RA-BDNF differentiated SH-SY5Y cells. Tau phosphorylation increased at all the examined sites ser-199, ser-202, thr-205, ser-396, and ser-404, all of which are hyperphosphorylated in AD brain. We also investigated whether GSK3beta, Cdk5 or JNK was involved in tau phosphorylation in the differentiated SH-SY5Y cells. We found that GSK3beta contributed most and that Cdk5 made a minor contribution. JNK was not involved in tau phosphorylation in this system. The GSK3beta-inhibitor, lithium, inhibited tau phosphorylation in a concentration-dependent manner and with good reproducibility, which enables ranking of substances in this cell model. RA-BDNF differentiated SH-SY5Y cells could serve as a suitable model for studying the mechanisms of tau phosphorylation and for screening potential GSK3beta inhibitors.
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PMID:The retinoic acid and brain-derived neurotrophic factor differentiated SH-SY5Y cell line as a model for Alzheimer's disease-like tau phosphorylation. 1518 80

Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) has a characteristic chimeric oncogene EWS-FLI1, which results from chromosomal translocation t (11; 22), that is believed to initiate tumorigenesis of EWS/PNET. However, the specific details of EWS/PNET oncogenesis and exact role of EWS-FLI1 remain largely unknown. In this study we explored the role of EWS-FLI1 in tumor differentiation using an embryonal carcinoma cell line P19 as a model, with forced expression of EWS-FLI1 in these cells. EWS-FLI1 has been reported to promote neural differentiation in fibroblasts, mesenchymal stem cells and rhabdomyosarcoma cells. We show forced expression of EWS-FLI1 causes absence of retinoic acid-induced neural morphology, and decreases expression of neural-specific proteins MAPT and NCAM. Critical transcriptional factors for neural differentiation and stem cells are also altered in the presence of EWS-FLI1, including decreases in levels of Oct-3 and Pax-6, and an increase in the level of Id2, which is a target of EWS-FLI1. Increased proliferation and decreased apoptotic rates are also observed in P19 cells with forced expression of EWS-FLI1. Our results raise the possibility that arrest of neural differentiation by forced expression of EWS-FLI1 as observed in this study may result from dysregulation of the cell cycle and cell proliferation. Taken together, our results demonstrate that the modulation of neural differentiation in P19 cells which have a stem cell-like pluripotency in vitro can provide a novel model system to study the neural differentiation effects of EWS-FLI1 tumorigenesis of EWS/PNET.
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PMID:Neural differentiation arrest in embryonal carcinoma cells with forced expression of EWS-FLI1. 1862 80

Neuroscience, including research on Alzheimer's disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta1, nerve growth factor, and vitamin D3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimer's disease field.
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PMID:An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells with morphological and biochemical characteristics of mature neurons. 2041 90


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