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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 223-233 
    ISSN: 1573-6830
    Schlagwort(e): tau ; kinases ; signal transduction ; Alzheimer's disease ; phosphorylation ; paired helical filaments
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract 1. The individual and sequential influence of protein kinase C (PKC), protein kinase A (PKA) and mitogen-activated protein kinase (MAP kinase) on human brain tau was examined. 2. A range of PKC concentrations generated certain phosphoepitopes common with paired helical filaments. These epitopes were masked by higher PKC concentrations, suggesting the presence of multiple tau phosphorylation sites for which PKC exhibited differing affinities and/or conformational alterations in tau induced by sequential PKC-mediated phosphorylation. 3. Prior phosphorylation by PKC enhanced the nature and extent of AD-like tau antigenicity generated by subsequent incubation with MAP kinase yet inhibited that generated by subsequent incubation with PKA. 4. Dephosphorylation of tau prior to incubation with kinases significantly altered the influence of individual and multiple kinase incubation on tau antigenicity in a site-specific manner, indicating that prior in situ phosphorylation events markedly influenced subsequent cell-free phosphorylation. 5. In addition to considerations of the potential impact of tau phosphorylation by individual kinases, these findings extend previous studies which indicate that tau antigenicity, and, presumably, its behavior in situ, is influenced by the sequential and convergent influences of multiple kinases.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1573-6830
    Schlagwort(e): MAP kinase ; tau ; protein kinase C ; wortmannin ; PD98059 ; neuroblastoma ; Alzheimer's disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract Mitogen-activated protein (MAP) kinase phosphorylates tau in cell-free analyses, but whether or not it does so within intact cells remains controversial. In the present study, microinjection of MAP kinase into SH-SY-5Y human neuroblastoma cells increased tau immunoreactivity toward the phosphodependent antibodies PHF-1 and AT-8. In contrast, treatment with a specific inhibitor of MAP kinase (PD98059) did not diminish “basal” levels of these immunoreactivities in otherwise untreated cells. These findings indicate that hyperactivation of MAP kinase increases phospho-tau levels within cells, despite that MAP kinase apparently does not substantially influence intracellular tau phosphorylation under normal conditions. These findings underscore that results obtained following inhibition of kinase activities do not necessarily provide an indication of the consequences accompanying hyperactivation of that same kinase. Several studies conducted in cell-free systems indicate that exposure of tau to multiple kinases can have synergistic effects on the nature and extent of tau phosphorylation. We therefore examined whether or not such effects could be demonstrated within these cells. Site-specific phospho-tau immunoreactivity was increased in additive and synergistic manners by treatment of injected cells with TPA (which activates PKC), calcium ionophore (which activates calcium-dependent kinases), and wortmannin (which inhibits PIP3 kinase). Alteration in total tau levels was insufficient to account for the full extent of the increase in phospho-tau immunoreactivity. These additional results indicate that multiple kinase activities modulate the influence of MAP kinase on tau within intact cells.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular neurobiology 20 (2000), S. 497-508 
    ISSN: 1573-6830
    Schlagwort(e): tau ; phosphorylation ; signal transduction ; protein kinase C ; Alzheimer's disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract 1. The potential functions of the microtubule-associated protein tau have been expanded by the recent demonstration of its interaction with the plasma membrane. Since the association of tau with microtubules is regulated by phosphorylation, herein we examine whether or not the association of tau with the plasma membrane is also regulated by phosphorylation. 2. A range of tau isoforms migrating from 46 to 64 kDa was associated with crude particulate fractions derived from SH-SY-5Y human neuroblastoma cells, and were retained during the initial stages of plasma membrane purification. During the extensive washing utilized in purification of the plasma membrane, portions of each of these isoforms were depleted from the resultant purified membrane. Immunoblot analysis with phospho-dependent and -independent antibodies revealed selective depletion of phospho isoforms during membrane washing. This effect was more pronounced for the slowest-migrating (64-kDa) tau isoform. 3. This putative influence of phosphorylation on the association of tau with the plasma membrane was further probed by transfection of SH-SY-5Y human neuroblastoma cells with a tau construct that could associate with the plasma membrane but not with microtubules. Treatment with phorbol ester or calcium ionophore, both of which increased phospho-tau levels within the cytosol and plasma membrane, was accompanied by the dissociation of this tau construct from the membrane. 4. These data indicate that phosphorylation regulates the association with the plasma membrane. Dissociation from the membrane by phosphorylation may place tau at risk for hyperphosphorylation and ultimate PHF formation in a manner previously considered for tau dissociated from microtubules.
    Materialart: Digitale Medien
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  • 4
    ISSN: 0362-2525
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Medizin
    Notizen: The effect of removal of the liver has been noted in fishes, frogs, and turtles. As in the higher vertebrates, removal of the liver produced a fall in blood sugar and a loss in muscular tone. The lower vertebrates failed to respond to intravenous injections of glucose, as do the birds and mammals. They also fail to respond to maltose or levulose. The liver maintained the blood-sugar level in the lower vertebrates, which is necessary for the maintenance of life.The mechanism of carbohydrate metabolism in the lower vertebrates may be different from that in the higher ones, in that glucose, when injected intravenously, apparently exercises a progressively less beneficial effect on the characteristic hypoglycemic condition which follows the removal of the liver of mammals and cold-blooded vertebrates.
    Zusätzliches Material: 2 Tab.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 22 (1992), S. 81-91 
    ISSN: 0886-1544
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Medizin
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    ISSN: 0003-276X
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The applicability of the four-parameter model for physiological responses to the prediction of food intake and corresponding weight gain and individual organ weight gain was studied further in 40-day postpartum male rats. Seven groups of animals were maintained on diets in which protein content ranged from 0 to 23.54% casein. Food intake and weight gain were recorded every other day for each animal for 21 days. At the termination of the experiment the following organs were removed and weighed: liver, heart, lungs, spleen, kidneys, adrenals, and testes. When these weight values are fitted by use of the four-parameter model, food intake and total animal and organ weight gains can be predicted in relation to the amount of protein in the diet. It was found that liver, heart, lungs, spleen, and whole animal had similar K(0.5) values. However, it was also shown that there is variation in response of organs when relating organ weight as a percentage of body weight. For example, heart, lungs, and testes show an increased ratio on low protein diet while liver, kidneys, and adrenals maintain a fairly constant ratio and the spleen shows a decreased ratio. Additionally, it was noted that the animals on low protein diet consumed more food per gram body weight but did so at a slower rate. Possible future applications of the four-parameter model for physiological reponses are discussed.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 7
    ISSN: 0003-276X
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: The sex differential in coronary heart disease is well documented but poorly understood. Previous studies have demonstrated receptors for dihydrotestosterone (DHT) in the myocardium and smooth muscle cells of arteries from a number of species. In this autoradiographic study, we further investigated and characterized the in vivo uptake and retention of the androgen binding in the male baboon. Adult castrated male baboons were injected with 1 μg/kg bw 3H-testosterone; 1 hr after the injection, the animals were rapidly exsanguinated while under anesthesia. The heart and arterial system were removed and processed for autoradiography. As a negative control, one animal received both 3H-testosterone and 100-fold unlabeled testosterone. For positive controls, the pituitary gland, prostate, seminal vesicles, and other tissues were also removed and processed for autoradiography. In contrast to our previous finding with 3H-DHT, no nuclear uptake and retention of 3H-steroid was found in any of the cells in either the heart or the arterial system. In the positive control tissues, pituitary gland, prostate, seminal vesicles, and others, a very distinct nuclear uptake and retention of 3H-steroid was observed, which was completely inhibited by the simultaneous injection of 100-fold unlabeled testosterone. In the binding study, Scatchard analysis of the cytosol prepared from a 17-year-old female baboon demonstrated levels of androgen receptor (as determined by the use of radiolabeled R1881) comparable to that found in young adults. The results of these studies suggest that, in contrast to the generally accepted hypotheses, (1) circulating DHT, not testosterone, is the androgenic hormone that interacts with the cardiovascular tissue of the baboon and (2) there are separate receptors for testosterone and DHT in different tissues rather than a single receptor capable of binding both steroids.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
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  • 8
    ISSN: 0003-276X
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Zusätzliches Material: 3 Ill.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 38 (1928), S. 273-291 
    ISSN: 0003-276X
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 10
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    American Journal of Anatomy 162 (1981), S. 369-382 
    ISSN: 0002-9106
    Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: Previous studies on ultrastructural changes that occur in cultured human fibroblasts during their in vitro life-span indicate that “senescent” cells characteristically possess structurally altered mitochondia, highly lobed nuclei, and an abundance of secondary lysosomes when compared to early passage cells. In the present study, we demonstrate that improper preparative methods can induce altered mitochondrial morphology in preparations of both IMR-90 and HF730A fibroblasts, regardless of passage level. We also show that nuclei of both living and fixed IMR-90 fibroblasts are ovoid in shape, not lobulate, in well-spread cells, regardless of either the passage level or the proliferative capacity of the cell. Fibroblasts contain lobulated nuclei only when they have not spread completely on the culture substrate. Lobulations can be induced at any passage level by collagenase/trypsin or trypsin/EDTA treatment prior to fixation, but not by cytochalasin B treatment or by cold temperatures. We conclude that any treatment that affects cytoskeleton-membrane-culture substrate interactions will induce this aberrant nuclear morphology, but that this is not indicative of “senescence” and does not relate to proliferative decline.
    Zusätzliches Material: 18 Ill.
    Materialart: Digitale Medien
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