Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sequential activation of L-selectin and beta 2-integrins on neutrophils is crucial for the rolling, adherence and subsequent migration of these cells on the endothelium. However, little is known about a possible interplay between these adhesion receptors in the final regulation of cell motility. The results presented here show that sulfatides themselves (here used as tools to activate L-selectins), have no major effect on the cellular content of filamentous actin (F-actin), but cause a time-related decrease in the beta 2-integrin-induced formation of F-actin. This effect of sulfatides was abolished in cells lacking L-selectin as a result of pretreatment with chymotrypsin. A similar sulfatide-induced activation of L-selectin also caused a pronounced and time-related decrease of a subsequent chemotactic peptide-induced F-actin response. The effect of sulfatides on both beta 2-integrin- and chemotactic peptide-induced F-actin were abolished if L-selectin were blocked by preincubating the cells with specific antibodies to L-selectin. These effects of L-selectin engagement on cellular F-actin content were neither abolished by blocking the cytosolic free Ca2+ signal with bis-(2-amino-5-methylphenoxy)ethane-N,N,N',N'-tetraaceticacid tetraacetoxymethyly ester (MAPT/AM) nor by blocking a cAMP-induced activation of protein kinase A by pretreating the cells with adenosine-3',5'-cyclic monophos-phorothioate (Rp-cAMPS). Instead we found that L-selectin engagement impaired an early beta 2-integrin-induced tyrosine kinase activation, an event shown to be necessary for a normal beta 2-integrin-mediated F-actin response. The present demonstration of a negative feed-back function of L-selectin on beta 2-integrin-induced modulations of the actin cytoskeleton, suggests that the relative distribution and/or density of the respective L-selectin and beta 2-integrin ligands on endothelial cells might be important factors in determining the final site of firm adhesion and extravasation of neutrophils.
J Cell Sci 1996 Sep
PMID:Engagement of L-selectin impairs the actin polymerizing capacity of beta 2-integrins on neutrophils. 888 85

Cyclin-dependent kinase 5 (CDK5) is one of the cyclin-dependent kinases, and is expressed in mature neurons. CDK5 has been postulated to be a neurofilament or tau protein kinase, because it phosphorylates neurofilaments and tau protein (microtubule-associated protein tau) in vitro. It has been reported that CDK5 was immunohistochemically detected only in axons of neurons. We here report the immunohistochemical study of CDK5 using two distinct antibodies, one recognizing the N-terminal of CDK5 and the other the C-terminal. Immunoreactivity of CDK5 was found not only in axons, but also intensively in nuclei, though not in nucleoli, of neurons in the mouse central and peripheral nervous systems. The nuclear CDK5 possibly has a physiological function distinct from the neurofilament or tau protein kinase.
Brain Res 1996 Sep 02
PMID:Intracellular localization of cyclin-dependent kinase 5 (CDK5) in mouse neuron: CDK5 is located in both nucleus and cytoplasm. 889 Dec 82

Levels of the microtubule-associated protein tau in cerebrospinal fluid (CSF-tau) were measured in samples from 87 patients with Alzheimer's disease (AD), 114 patients with non-AD neurological diseases, and 22 normal control subjects, by sandwich enzyme-linked immunosorbent assay. The CSF-tau level was significantly higher in patients with AD than in patients with non-AD neurological diseases and in controls. High CSF-tau levels were found irrespective of age at onset, apolipoprotein E genotype, clinical stage, and ethnic group. Western blots of AD CSF proteins revealed two to three immunoreactive bands with apparent molecular mass between 50 and 65 kDa, which is consistent with phosphorylated CSF-tau. These results suggest that CSF-tau reflects progressive accumulation of tau due to the progressive death of neurons in the AD brain. Assay of CSF-tau may prove to be a reliable diagnostic test for AD.
Nihon Ronen Igakkai Zasshi 1996 Sep
PMID:[Tau protein in cerebrospinal fluid--a potential marker of Alzheimer's disease]. 894 Aug 64

Recent evidence suggests that beta-amyloid peptide (beta-AP) may induce tau protein phosphorylation, resulting in loss of microtubule binding capacity and formation of paired helical filaments. The mechanism by which beta-AP increases tau phosphorylation, however, is unclear. Using a hybrid septal cell line, SN56, we demonstrate that aggregated beta-AP(1-40) treatment caused cell injury. Accompanying the cell injury, the levels of phosphorylated tau as well as total tau were enhanced as detected immunochemically by AT8, PHF-1, Tau-1, and Tau-5 antibodies. Alkaline phosphatase treatment abolished AT8 and PHF-1 immunoreactivity, confirming that the tau phosphorylation sites were at least at Ser(199/202) and Ser396. In association with the increase in tau phosphorylation, the immunoreactivity of cell-associated and secreted beta-amyloid precursor protein (beta-APP) was markedly elevated. Application of antisense oligonucleotide to beta-APP reduced expression of beta-APP and immunoreactivity of phosphorylated tau. Control peptide beta-AP(1-28) did not produce significant effects on tau phosphorylation, although it slightly increased cell-associated beta-APP. These results suggest that betaAP(1-40)-induced tau phosphorylation may be associated with increased beta-APP expression in degenerated neurons.
J Neurochem 1997 Sep
PMID:Beta-amyloid-induced neurotoxicity of a hybrid septal cell line associated with increased tau phosphorylation and expression of beta-amyloid precursor protein. 928 19

Ceramide has been recently proposed to be a signal mediator in several important physiological processes including apoptosis, cellular growth, and differentiation. Because the microtubule-associated protein tau plays an important role in the establishment and maintenance of neuronal morphology, the effects of ceramide on tau were examined. Treatment of differentiated PC12 cells with the cell-permeable ceramide derivative N-acetylsphingosine (C2) resulted in a significant reduction in tau levels. Significant decreases in tau levels were also observed when the cells were treated with another ceramide derivative, N-hexanoylsphingosine (C6). In addition, C2 treatment increased the levels of a calpain-derived spectrin breakdown product but did not alter the levels of two cytoskeletal proteins, alpha-actin and alpha-tubulin. Because both tau and spectrin are proteolyzed in vitro by the calcium-activated cysteine protease calpain, the effects of ceramide analogues on the activity of this protease were examined. Treatment of PC12 cells with C2 enhanced calcium-stimulated proteolytic activity significantly, as revealed by monitoring the hydrolysis of the membrane-permeable calpain-selective fluorescence probe N-succinyl-L-leucyl-L-leucyl-L-valyl-L-tyrosine-7-amido-4-methylcoumarin . This activity increase was not due to a direct effect of C2 on calpains, because C2 did not alter the activities of purified calpain I or II. In addition, C2 treatment of PC12 cells resulted in a significant increase in the levels of calpain I and, to a lesser extent, the levels of calpastatin (an endogenous calpain inhibitor protein), whereas the levels of calpain II were not changed. Moreover, treatment of the cells with the synthetic calpain-specific inhibitor N-carbobenzoxy-L-leucyl-L-leucyl-L-tyrosine diazomethyl ketone blocked the C2-induced decreases in tau levels. These results indicate that tau levels are regulated in response to a physiological factor and, thus, have implications for ceramide-mediated changes in normal and pathological neuronal processes.
J Neurochem 1997 Sep
PMID:Ceramide selectively decreases tau levels in differentiated PC12 cells through modulation of calpain I. 928 24

Immunohistochemical and biochemical analyses of hyperphosphorylated tau proteins, the major component of neurofibrillary tangles, were performed in different brain regions from patients presenting with postencephalitic parkinsonism. Neurofibrillary tangles were found in hippocampus, neocortical areas (mostly in supragranular layers), and several subcortical structures. By immunoblotting, a tau protein triplet similar to the one seen in Alzheimer's disease was observed. This biochemical approach allows for the definition of postencephalitic parkinsonism from certain neurodegenerative disorders such as progressive supranuclear palsy and corticobasal degeneration.
Ann Neurol 1997 Sep
PMID:Pathological tau proteins in postencephalitic parkinsonism: comparison with Alzheimer's disease and other neurodegenerative disorders. 930 57

In order to clarify the manner and significance of tau expression in glial cytoplasmic inclusions (GCIs), ubiquitinated oligodendroglial abnormal structures in multiple system atrophy (MSA), an immunohistochemical study was carried out in the lesions of the pontine nuclei of 10 cases of MSA using antibodies against various epitope locations of tau protein. As a result, tau-2 was constantly but weakly positive in ubiquitinated GCIs in each case (from 28.6 to 66.7%). However, tau-2-immunoreactivity in GCIs was not correlated to the density of ubiquitin-positive GCIs or preserved pontine neurons. Antibodies against tau proteins of N-terminal or C-terminal failed to label GCIs, although a few number of GCIs were occasionally positive for tau-1 after dephosphorylation. In comparison with the knowledge on tau-immunoreactivity of coiled bodies (CBs) in oligodendroglia in progressive supranuclear palsy (PSP) or corticobasal degeneration, GCIs are quite different from CBs which have a wide range of epitope location of tau proteins, including N-terminal and C-terminal. This study suggests that expression of tau proteins in GCIs is not related to the essential neurodegenerative process in MSA but induced by non-specific stress in oligodendroglia, unlike CB in various 'tau diseases' such as PSP.
Neurosci Lett 1997 Sep 26
PMID:Tau immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. 934 47

Nitric oxide (NO.) can induce transient [Ca2+] changes in endothelial cells not different from receptor mediated signalling. Whether this Ca2+ signal may provide a link with IL-8 secretion induced by NO. donors was investigated in human endothelial cells. Sodium nitroprusside (SNP) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) dose dependently increased IL-8 production in this cell type. Additive IL-8 secretion was found with TNFalpha. Buffering intracellular Ca2+ with MAPT/AM suppressed NO. induced [Ca2+]i changes and reduced subsequent IL-8 secretion. The additive effect of both NO. donors on TNFalpha induced IL-8 secretion was completely blocked in the presence of MAPT/AM. SKF 96365, which has been shown to block receptor mediated Ca2+ entry, and TMB-8, which blocks intracellular Ca2+ release, both inhibited IL-8 secretion, particularly when TNFalpha was used as a costimulator, indicating that [Ca2+]i changes are important components of IL-8 induction by NO..
FEBS Lett 1997 Sep 29
PMID:Intracellular Ca2+ dependence of nitric oxide mediated enhancement of interleukin-8 secretion in human endothelial cells. 935 Sep 89

Observations from ultrastructural and immunohistochemical studies suggest that spongiform lesions in the gerbil cochlear nucleus are derived principally from dendrites. Almost one-fifth of the lesion profiles examined ultrastructurally exhibited synaptic contacts with axon terminals. In addition, approximately 80% of lesions are immunopositive for the dendrite-specific microtubule associated protein, MAP2. Ultrastructural studies showed a small percentage (8%) of lesions were derived from myelinated axons, although none were immunohistochemically labelled with antibodies to the tau protein. Staining with the astrocyte-specific markers GFAP, S-100 and vimentin yielded equivocal results, but did not support a major role for astrocytes in lesion formation. The histological profile matches that seen in some other well characterized types of spongiform degeneration.
J Neurocytol 1997 Sep
PMID:Spongiform degeneration of the gerbil cochlear nucleus: an ultrastructural and immunohistochemical evaluation. 935 48

This study examined the phosphorylation of tau on Ser 262, within the first microtubule-binding domain, by a developmentally regulated 100 kDa protein kinase exhibiting significantly greater activity in the embryonic rat brain than in the adult rat brain. This protein kinase co-purified with microtubules and co-immunoprecipitated with both tau and MAP-2. In addition to phosphorylating tau, MAP-2, and a Ser 262-containing peptide, the present protein kinase activity was shown to autophosphorylate as determined by the in-gel kinase assay in the absence of any protein or peptide polymerized into the matrix. Phosphorylation of tau with this protein kinase significantly reduced the tau-microtubule interaction, and the effect was significantly greater with microtubule-associated protein (MAP) preparations from embryonic brain than with preparations from the adult. Ser 262 is phosphorylated extensively in paired helical filament (PHF) tau from Alzheimer's disease (AD) brain, to a lesser extent in fetal tau, and only to a very minor extent in biopsy-derived human tau. Because the 100 kDa protein kinase activity phosphorylates Ser 262 and is higher in the fetal brain than the adult brain, it is hypothesized that an inappropriate re-expression and/or re-activation of this or a similar developmentally regulated protein kinase could contribute to the phosphorylation of Ser 262 in PHF-tau, and thus play a role in the pathogenesis of AD.
Brain Res 1997 Sep 05
PMID:Phosphorylation of microtubule-associated protein tau on Ser 262 by an embryonic 100 kDa protein kinase. 936 62


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