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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 82 (2002), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We assayed levels of lipid peroxidation, protein carbonyl formation, glutamine synthetase (GS) activity and both oxidized and reduced glutathione to study the link between oxidative damage, aging and β-amyloid (Aβ) in the canine brain. The aged canine brain, a model of human brain aging, naturally develops extensive diffuse deposits of human-type Aβ. Aβ was measured in immunostained prefrontal cortex from 19 beagle dogs (4–15 years). Increased malondialdehyde (MDA), which indicates increased lipid peroxidation, was observed in the prefrontal cortex and serum but not in cerebrospinal fluid (CSF). Oxidative damage to proteins (carbonyl formation) also increased in brain. An age-dependent decline in GS activity, an enzyme vulnerable to oxidative damage, and in the level of glutathione (GSH) was observed in the prefrontal cortex. MDA level in serum correlated with MDA accumulation in the prefrontal cortex. Although 11/19 animals exhibited Aβ, the extent of deposition did not correlate with any of the oxidative damage measures, suggesting that each form of neuropathology accumulates in parallel with age. This evidence of widespread oxidative damage and Aβ deposition is further justification for using the canine model for studying human brain aging and neurodegenerative diseases.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 33 (1964), S. 235-258 
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of inherited metabolic disease 11 (1988), S. 221-228 
    ISSN: 1573-2665
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chediak-Higashi syndrome (CHS) cells have been previously observed to exhibit several of the same characteristics as those of xeroderma pigmentosum (XP) and xeroderma pigmentosum variants. Cultured CHS fibroblasts have been examined for altered responses in both depletion of NAD and elevation of diadenosine-5′,5‴-tetraphosphate (Ap4A) following DNA damage since both responses have been reported as altered in XP cells and since Ap4A has been reported as absent from the platelets of CHS patients. Lowering of NAD following UV irradiation occurred in CHS cells in a manner similar to that of control and XP variant cells, but different from that of XP cells. CHS fibroblasts were not found to be deficient in Ap4A and exhibit basal levels very similar to those of control fibroblasts. No change in Ap4A pools were observed which correlated with cell growth, in contrast to previously published reports. Furthermore, while Ap4A levels are not elevated in XP cells, we observe an elevation of Ap4A pools in CHS cells which mimics the elevations observed in control and XP variant cells. We conclude that: (1) CHS cells more closely resemble control or XP variant cells than XP cells with regard to NAD lowering and Ap4A elevation following UV irradiation; (2) the photosensitivity exhibited by CHS cells is not due to general defects in the synthesis of poly(ADP-ribose) from NAD or in Ap4A metabolism; and (3) alteration of Ap4A pool size in CHS fibroblasts is inappropriate as a biochemical marker for CHS.
    Type of Medium: Electronic Resource
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