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  • 1
    Electronic Resource
    Electronic Resource
    Aberrant Phosphoinositide Metabolism in Alzheimer's Disease (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 695 (1993), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: Since phosphoinositide-specific phospholipase C (PLC) is one of the key molecules in signal transduction, its involvement was assessed in Alzheimer's disease (AD). The phosphatidyl-inositol (PI)-specific PLC activity in the Alzheimer cytosolic and participate fractions was not significantly different from that in the control fractions. The PI-specific PLC activity as a function of the free Ca2+ concentration was also similar between control and Alzheimer brains. These results suggest that the PI-specific PLC activity is not altered in AD. Immunostaining of a specific antibody against the PLC isozyme, PLC-δ, demonstrated that this enzyme was abnormally accumulated in neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores, and neuropil threads in AD brains. Western blot analysis confirmed that PLC-δ was concentrated in the paired helical filament (PHF)-rich fraction of AD brains. PLC-δ marked the same neurons containing τ immunoreactivity and yet τ and PLC-δ often marked different structures within the same neuron, with τ more clearly on NFT and PLC-δ covering it superficially. The double stain with PLC-δ and basic fibroblast growth factor (bFGF) binding suggest that PLC-δ is an intracellular marker, showing little overlap with bFGF binding, an extracellular marker. All of this was consistent with the electron microscopy, with PLC-δ being NFT associated. Antibodies to other PLC isozymes did not produce positive immunostaining of these pathologic structures. Moreover, diffuse and amorphous deposits of PLC-δ were found to precede the accumulation of fibrillary deposits. These results suggest that PLC-δ accumulation plays a possible role in the formation of intraneuronal inclusions in AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1993.tb23025.x
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of overexpression of very low density lipoprotein receptor on cell growth (2000)
    Springer
    Heart and vessels 15 (2000), S. 74-80 
    Details
    ISSN: 1615-2573
    Keywords: Key words Very low density lipoprotein receptor ; COS-7 cell ; Cell growth ; Lipid accumulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The very low density lipoprotein (VLDL) receptor is a member of the LDL receptor gene family and binds only apoE-containing lipoproteins. Although the VLDL receptor has been shown to play an important role in the proliferation of vascular smooth muscle cells and the formation of foam cells as primary responses of atherogenesis, its actual functions are still unclear. To understand the biological roles of the VLDL receptor in foam cell formation and cell growth, we tried to overexpress VLDL receptors in various cells. When COS-7 cells were transfected with an expression plasmid containing VLDL receptor cDNA, cell growth was inhibited by overexpression of the receptor and this growth inhibition was ligand-independent. The O-linked glycosylation region, but not the cytoplasmic domain, of the receptor appeared to be responsible for this growth inhibition. On the other hand, VLDL receptor expression induced enhanced incor-poration of lipids and cytoplasmic enlargement. These changes were dependent on the exogenous ligand and the cytoplasmic domain of the receptor. These results suggest that the VLDL receptor functions as a regulator of cell growth and differentiation, which may be distinct from its lipid-incorporating function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003800070035
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  • 3
    Electronic Resource
    Electronic Resource
    Enhanced phosphoinositide metabolism in colorectal carcinoma cells derived from familial adenomatous polyposis patients (1994)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 55 (1994), S. 477-485 
    Details
    ISSN: 0730-2312
    Keywords: phospholipase C ; inositol trisphosphate ; diacylglycerol ; tyrosine kinase ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The production of the second messenger molecules diacylglycerol and inositol 1,4,5-trisphosphate is mediated by activated phosphatidylinositol-specific phospholipase C (PLC) enzymes. We report the enhancement of the phosphoinositide metabolism pathway in KMS-4 and KMS-8 cells, both of which are human colorectal carcinoma cell lines derived from familial adenomatous polyposis patients. In these cells, the cellular contents of diacylglycerol and inositol 1,4,5-trisphosphate were constitutively increased and the PLC activity in vitro was significantly high, as compared with those in normal colon cells or in other sporadic colorectal carcinoma cells. Northern and Western analyses showed the high expression levels of both PLC-γ1 and PLC-δ1 in KMS-4 and KMS-8 cells. Moreover, we detected the enhancement of protein-tyrosine kinase activity and tyrosine phosphorylation of PLC-γ1 in these KMS cells. These results suggest the involvement of activated phosphoinositide signaling pathways in the colorectal tumorigenesis of familial adenomatous polyposis. © 1994 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240550407
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