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Pyroglutamate-modified amyloid β-peptides – AβN3(pE) – strongly affect cultured neuron and astrocyte survival (2002)

Russo, Claudio ; Violani, Elisabetta ; Salis, Serena ; [et al.]

Oxford, UK : Blackwell Science Ltd

Journal of neurochemistry 82 (2002), S. 0

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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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Influence of culture conditions on monoamine oxidase A and B activity in rat astrocytes (1996)

Carlo, Pia ; del Rio, Meris ; Violani, Elisabetta ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Cell Biochemistry and Function 14 (1996), S. 19-25

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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.