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At least 37 records · Page 2Linked to original sources
PubMed1979

Differences in surface morphology of microtubules reconstituted from pure brain tubulin using two different microtubule-associated proteins: the high molecular weight MAP 2 proteins and tau proteins.

Microtubules were reconstituted from homogeneous brain tubulin and homogeneous preparations of two different microtubule associated proteins, the high molecular weight MAP 2 proteins or the tau proteins. The resulting microtubules were characterized by three electron microscopical procedures: Thin sectional analysis of embeded material, negative staining analysis using a STEM microscope and high resolution metal-shadowing analysis. By all three procedures MAP 2 microtubules have a much rougher surface morphology than tau microtubules, in agreement with the much higher molecular weight of the MAP 2 proteins. Tau microtubules, however, do not show the very smooth surface of microtubules assembled from pure tubulin in the absence of any microtubule associated proteins. In the case of MAP 2 microtubules thin sectional analysis as well as metal shadowing reveals that the globular protrusions seen in negative staining analysis appear as linear side arms which may extend by as much as 30 nm on both sides from the microtubular wall proper, giving rise to an overall structure with a diameter close to 100 nm. The possible implication of such structures for in vivo situations is briefly discussed as is the possibility that the "halo-effect" around microtubules seen in vivo may be due to a structural organization similar to that of MAP 2 tubules in vitro.

Animals↗
PubMed2026

Subchronic benzo[a]pyrene exposure disrupts APOE4-regulated lipid metabolism to induce Tau hyperphosphorylation and cognitive deficits.

BACKGROUND: Benzo[a]pyrene (B[a]P) is both a carcinogen and a potent neurotoxic pollutant. Despite growing evidence linking B[a]P to neurological dysfunction, the responsible mechanisms have not been elucidated. METHODS: Here, we employed human apolipoprotein E4 (hAPOE4) transgenic mice and APOE knockout (APOE-KO) mice to evaluate the influence of APOE on B[a]P-mediated neurotoxicity. hAPOE4 mice overexpress the human APOE4 isoform, whereas APOE-KO mice lack APOE expression; wild-type C57BL/6 J mice served as controls. Animals received intraperitoneal injections of B[a]P at 0, 2.5, or 6.25 mg/kg on alternate days for 3 months. Spatial memory and learning were examined via Morris Water Maze (MWM). Neuronal morphology, including dendritic branching and spine density in the CA1 region of the hippocampus and dentate gyrus (DG), was assessed using Golgi-Cox staining. Neurofibrillary tangles were detected by silver glycine staining. Tau, phosphorylated Tau (Ser199 and Ser396), and LRP1 were evaluated using Western blot and immunohistochemical analyses. Chromatin immunoprecipitation PCR (ChIP-PCR) was undertaken to examine the regulation of APOE4 expression by the aryl hydrocarbon receptor (AHR). In addition, both untargeted metabolomics and lipidomics analyses were conducted following B[a]P exposure. RESULTS: B[a]P led to pronounced impairments in mouse spatial memory and learning, shown by greater escape latency, less time in the target quadrant, and a decreased number of platform crossings in MWM tests. Structural analyses revealed a significant reduction in dendritic branching within the hippocampal CA1 and DG regions. These neurobehavioral and morphological deficits were most severe in hAPOE4 mice, which displayed greater cognitive impairment and more extensive dendritic loss than B[a]P-treated wild-type mice, indicating that APOE4 amplifies B[a]P-induced neurotoxicity. ChIP assays demonstrated that B[a]P modulates APOE4 transcription through AHR-dependent mechanisms. Additionally, metabolomics and lipidomics analyses revealed widespread B[a]P-induced metabolic remodeling, suggesting that disrupted lipid metabolism and altered neuronal membrane integrity may contribute to the observed neurotoxicity and cognitive dysfunction. CONCLUSION: Collectively, the results indicate that B[a]P-mediated neurotoxicity may be facilitated, at least in part, by APOE4-dependent dysregulation of lipid metabolic pathways.

Animals↗
PubMed1976

The separation, identification, and quantitation of cannabinoids and their tau=butyldimethylsilyl, trimethylsilylacetate, and diethylphosphate derivatives using high-pressure liquid chromatography, gas-liquid chromatography, and mass spectrometry.

Methods for the separation, identification, and quantitation, of cannabinoids present in hashish have been developed. These methods include high-pressure liquid chromatographic and gas-liquid chromatographic separation of cannabinol, delta 9-tetrahydrocannabinol, delta 8-tetrahydrocannabinol, and cannabidiol as well as their tau-butyidimethylsilyl either and trimethylsilylacetate derivatives. The necessity for internal standards; the sensitivity of the HPLC method; and some mass spectral fragmentation pathways for the tau-butyldimethylsily, trimethylsilylacetate, and diethylphosphate derivatives are discussed.

Cannabinoids↗
PubMed1977

[Variation of the time constant (tau) of the decay of end-plate current during focalized transmitter release].

The variations of the time constant tau of the end-plate current (epc) have been studied at the clamped neuromuscular junction of the frog while transmitter release was focalised by local iontophoretic application of Ca++. In the absence of any anticholinesterasic drug, tau varies according to the variations of the intensity of epc (Iepc) due to pre or postsynaptic experimental procedure. It is suggested that focalisation of transmitter release induces local acetylcholinesterase inhibition by an excess of substrate; then the transmitter life time in the synaptic cleft is momentarily increased, allowing repeated binding of Ach to postsynaptic receptors.

Acetylcholinesterase↗
PubMed2026

A complex of MAST1 and 14-3-3η regulates Tau phosphorylation in the developing cortex.

The MAST family of serine/threonine kinases has been implicated in a spectrum of human neurodevelopmental disorders. However, little is known about their biological function or regulation. Seeking to fill these gaps in our knowledge, we have identified upstream and downstream partners of MAST1. 14-3-3η, a neuronal 14-3-3 paralog, specifically interacts with MAST1 at two regulatory serines, S90 and S161. p21-activated kinase (PAK), a neuronal regulator of the actin cytoskeleton, phosphorylates MAST1 to regulate its interaction with 14-3-3η. Exploiting mouse models of human Mega-Corpus-Callosum Syndrome (MCC) and whole brain phosphoproteomics, we identify the microtubule-associated protein Tau as a candidate substrate of MAST1. We show that pathogenic MAST1 mutations perturb protein function either through misfolding or attenuation of kinase activity. Our data are consistent with a model in which the MAST kinases couple PAK, a neuronal regulator of the actin cytoskeleton, to microtubule remodeling during the differentiation and specification of cortical neurons.

Animals↗
PubMed1977

Cytochemical study of the lamellar bodies in the swimbladder of the toadfish Opsanus tau L.

The columnar epithelial cells of the gas gland in the swimbladder of the toadfish, Opsanus tau L., contain lamellar bodies that resemble the lamellar bodies found in epithelial cells of vertebrate lungs. Cytochemical assays indicate that swimbladder lamellar bodies are soluble in chloroform-methanol solution, react with tricomplex flocculation solution (indicating a phospholipid component), exhibit a positive reaction for cholesterol when exposed to digitonin, and contain acid phosphatase. The anterior chamber of the toadfish swimbladder is lined by an extracellular layer. Digitonin-cholesterol crystals are found in this layer when the swimbladder is treated with digitonin. A ruthenium red positive layer is also present in the anterior chamber of the toadfish swimbladder. The structure and cytochemistry of swimbladder lamellar bodies are compared with those of vertebrate lung lamellar bodies. Similarities between the extracellular layer in the swimbladder and the extracellular layer in lungs are also noted.

Acid Phosphatase↗
PubMed1975

DNA synthesis - dependent cell division of Escherichia coli 15 TAU after arginine and uracil starvation.

Extensive cell division after synchronization of Escherichia coli 15 TAU by arginine and uracil starvation occurs only when DNA synthesis is permitted to proceed by at least a short pulse of thymine applied between 30 and 60 min after transfer of synchronized culture to thymine-free medium with arginine and uracil. The time schedule of synchronized cell division in dependence on the schedule of intervals of DNA synthesis and inhibition of DNA synthesis was determined. The termination of replication cycles which were not completed to the very end during arginine and uracil starvation seems to be the decisive event for subsequent cell division after synchronization.

Arginine↗
PubMed1978

Isolation of tau-phosphohistidine from a phosphoryl-enzyme intermediate of human prostatic acid phosphatase.

The carbethoxylation of prostatic acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2) was accompanied by modification of histidine residues and the inactivation of the enzyme. These findings are consistent with photoinactivation experiments described earlier (Rybarska, J. and Ostrowski, W (1974) Acta Biochim, Polon. 21, 377--390). Prostatic acid phosphatase was phosphorylated at alkaline pH using p-nitrophenyl [32P]phosphate as substrate. Phosphoryl enzyme is stable in alkaline solutions and undergoes dephosphorylation at acidic pH. After hydrolysis of phosphoryl enzyme in strong alkaline solution, a single phosphoryl amino acid was isolated from hydrolyzate and identified as the tau-phosphohistidine.

Acid Phosphatase↗
PubMed1979

Studies on a membrane-bound and solubilized ribonucleotide reductase preparation from Escherichia coli TAU-.

Ribonucleotide reductase has been shown to be associated with the DNA-membrane complex in Escherichia coli TAU- cells. The membrane-bound enzyme has been released in a soluble form using a combined treatment of 1% sarcosyl (pH 8.0) and 1% sodium deoxycholate (pH 6.5). Allotropic differences in the modulatory effects of ATP, Mg2+, EDTA and dithiothreitol on the membrane-bound and solubilized enzyme activity are discussed.

Adenosine Triphosphate↗
PubMed1979

Renin response to hemorrhage and hypotension in the aglomerular toadfish Opsanus tau.

Renal renin and the juxtaglomerular cells evolved in primitive bony fishes, whereas the macula densa emerged later in vertebrate phylogeny. We attempted to determine whether a renal arteriolar baroreceptor exists in the toadfish Opsanus tau, which possess renin and granulated cells in the kidneys, but lack glomeruli and macula densa. Cumulative hemorrhage of 1.5, 3, 6, 12, and 18 ml/kg, or a single massive bleeding from unanesthetized toadfish, kept in 50% seawater, caused an immediate and significant decrease in mean aortic pressure and stepwise increases (5-20 times) of plasma renin activity (PRA). Papaverine (10 mg/kg) caused hypotension and increased PRA. Minoxidil (6-12 mg/kg) neither decreased blood pressure nor increased PRA. The results suggest that toadfish respond to hemorrhage and acute hypotension with renin release despite the absence of a macula densa. It remains to be determined whether decreased renal perfusion pressure due to decreased dorsal aortic pressure stimulated the receptor in the granulated cells or whether the renal nerves may be involved.

Angiotensinogen↗
PubMed1977

Vitamin B12 radioassay with oyster toadfish (Opsanus tau) serum as binder.

We describe a vitamin B12 radioassay in which oyster toadfish (Opsanus tau) serum is used as the binding protein. The serum is quite stable and has a high capacity and high binding affinity (K greater than 10(12) liter/mol) for vitamin B12. The binding is not significantly affected by temperature, the presence of denatured proteins, or the amount of vitamin B12 present. The radioassay is reproducible (CV 4.4%) within assay, 7.8% between assays) and sensitive (12 ng/liter). Assay accuracy is unaffected by the protein in serum or by reasonable variations in incubation temperature and time.

Animals↗
PubMed1979

Sounds evoked by brain stimulation in the oyster toadfish Opsanus tau L.

Various regions in the brains of anesthetized oyster toadfish were electrically stimulated. Temporal properties of evoked sounds formed a continuum from simple to complex. One-to-one responses (one sound pulse for each stimulus pulse) and buzzes, elicited by stimulation in the caudal medulla and cervical spinal cord, were simpler than natural sounds. Natural grunts vary from individual pulses to long variable interval series of pulses called growls. Grunts were elicited by stimulation in the diencephalon, midbrain, medulla, and spinal cord. Evoked grunt pulses varied in duration from short to long and series of grunts varied from individual pulses to bursts approaching a boatwhistle, the courtship call of the male. Boatwhistles were elicited in male as well as in one female fish by stimulation in medullary and midbrain areas. Sites evoking sound production appeared to be part of an integrated system so that boatwhistles and grunts could be evoked from a single stimulation in various parts of the brain.

Animals↗