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  • 1
    Electronic Resource
    Electronic Resource
    Pyroglutamate-modified amyloid β-peptides – AβN3(pE) – strongly affect cultured neuron and astrocyte survival (2002)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 82 (2002), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: N-terminally truncated amyloid-β (Aβ) peptides are present in early and diffuse plaques of individuals with Alzheimer's disease (AD), are overproduced in early onset familial AD and their amount seems to be directly correlated to the severity and the progression of the disease in AD and Down's syndrome (DS). The pyroglutamate-containing isoforms at position 3 [AβN3(pE)−40/42] represent the prominent form among the N-truncated species, and may account for more than 50% of Aβ accumulated in plaques. In this study, we compared the toxic properties, fibrillogenic capabilities, and in vitro degradation profile of Aβ1–40, Aβ1–42, AβN3(pE)−40 and AβN3(pE)−42. Our data show that fibre morphology of Aβ peptides is greatly influenced by the C-terminus while toxicity, interaction with cell membranes and degradation are influenced by the N-terminus. AβN3(pE)−40 induced significantly more cell loss than the other species both in neuronal and glial cell cultures. Aggregated AβN3(pE) peptides were heavily distributed on plasma membrane and within the cytoplasm of treated cells. AβN3(pE)−40/42 peptides showed a significant resistance to degradation by cultured astrocytes, while full-length peptides resulted partially degraded. These findings suggest that formation of N-terminally modified peptides may enhance β-amyloid aggregation and toxicity, likely worsening the onset and progression of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2002.01107.x
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of ten thiocompounds on rat liver DNA damage induced by a small dose of N-nitrosodimethylamine (1992)
    Springer
    Archives of toxicology 66 (1992), S. 286-290 
    Details
    ISSN: 1432-0738
    Keywords: N-Nitrosodimethylamine ; Thiocompounds ; Rat liver DNA damage ; Viscometric analysis of DNA fragmentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use in a chemoprevention study of high doses of the genotoxic agent might result in erroneous information because of possible nonlinearity of pharmacokinetic processes and toxicity-induced derangement of physiological defense mechanisms. According to these premises ten thiocompounds, potentially active as inhibitors of metabolic activation and/or scavengers, were examined for their capability of reducing the frequency of liver DNA lesions induced by a very small dose of N-nitrosodimethylamine (NDMA). This was accomplished by means of a viscometric technique previously found suitable to detect a minimal amount of DNA fragmentation. Rats were injected i.p. or i. v. with 1 mmol/kg of thiocompound, 0.2 mg/kg NDMA given by gavage 1 h afterwards, and killed for DNA damage assessment 14 h later. Statistically significant changes of viscometric parameters, which are considered indicative of a protective activity, were produced by disulfiram (DSF), and to a lower extent by diethyldithiocarbamate (DEDTC). Any modification of NDMA-induced DNA damage was absent in rats pretreated with glutathione reduced form (GSH) and dimethyl sulfoxide (DMSO). Allyl disulfide (ADS), L-cysteine (CYS), N-acetylcysteine (NAC), α-mercaptopropionylglycine (MPG), ethylxanthic acid (PEX), and 2-mercaptoethane sulfonic acid (MESNA) increased in various degree the frequency of DNA-strand breaks. In subsequent experiments the protective activity of DSF was found to be dose-related, dependent on the time of administration, and greater by oral route. Taken as a whole, these results suggest that several putative anticarcinogens might be ineffective against the DNA-damage produced by the low doses encountered in human exposure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02307175
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  • 3
    Electronic Resource
    Electronic Resource
    Influence of culture conditions on monoamine oxidase A and B activity in rat astrocytes (1996)
    New York, NY [u.a.] : Wiley-Blackwell
    Cell Biochemistry and Function 14 (1996), S. 19-25 
    Details
    ISSN: 0263-6484
    Keywords: astrocyte cultures ; monoamine oxidase A and B ; serum ; stripped serum ; chemically defined medium ; Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Astroglial cells dispersed from newborn rat hemispheres were established in medium supplemented with 20 per cent fetal calf serum (FBS) and then grown to a confluent monolayer in the presence of 10 per cent FBS or charcoal-stripped FBS (CS). Type 1 astrocytes were subcultured and either maintained under the same conditions of the primary cultures or converted to serum-free chemically defined medium (CDM). No differences were found in either MAO A or MAO B activity of astrocytes grown in the presence of FBS or CS after 15 and 21 days in vitro (day 1 and 6 of subculture). In contrast, on day 21 both MAO A and MAO B activities were markedly higher in astrocytes subcultured in CDM compared with cells maintained in serum-supplemented medium. This difference appeared to be due to increased number of enzyme molecules, since kinetic analysis showed an increase in Vmax of both MAO isoenzymes in serum-free medium, but no change in Km. Consistently, the recovery of MAO A and MAO B activity after irreversible enzyme inhibition by clorgyline and deprenyl was faster in CDM than in FBS-supplemented medium, indicating enhanced enzyme synthesis under serum-free condition. Estimates of half-lives for the recovery of MAO A and MAO B activity indicated that, under both culture conditions, type A activity had a higher turnover rate than type B. The effect of CDM on astrocyte MAO does not appear to be due to selection of a subpopulation of cells, but rather linked to a morphological change (differentiation) with increased synthesis of both MAO isoenzymes.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cbf.645
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