Studies of biochemical changes in cultured skin fibroblasts derived from sporadic and familial Alzheimer's disease individuals: qualitative and quantitative changes in double-stranded DNA-stimulated phosphorylation of endogenous nucleoproteins

Endogenous proteins phosphorylated in vitro with nuclear extracts prepared from skin fibroblasts of familial and sporadic AD subjects and age/sex-matched controls show qualitative/quantitative changes which were dependent upon the addition of natural and synthetic double-stranded DNA (dsDNA) to assa...

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Bibliographic Details
Published inBiochemistry and molecular biology international Vol. 31; no. 2; p. 279
Main Authors An, S, Wu, J M
Format Journal Article
LanguageEnglish
Published England 01.10.1993
Subjects
Alzheimer Disease - enzymology
Alzheimer Disease - genetics
Antibodies, Monoclonal
Blotting, Western
Cells, Cultured
DNA - pharmacology
Electrophoresis, Polyacrylamide Gel
Fibroblasts - enzymology
Humans
Molecular Weight
Nucleoproteins - metabolism
Phosphoproteins - metabolism
Phosphorylation
Poly dA-dT - pharmacology
Protein Kinases - metabolism
Skin
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Summary:Endogenous proteins phosphorylated in vitro with nuclear extracts prepared from skin fibroblasts of familial and sporadic AD subjects and age/sex-matched controls show qualitative/quantitative changes which were dependent upon the addition of natural and synthetic double-stranded DNA (dsDNA) to assay mixtures. Control and AD cell-free homogenates showed a pronounced increase in four proteins migrating with molecular weights of 180- (p180), 75-(p75), 65- (p65), and 34-kD (p34). Optimal stimulation of each protein required a different concentration of dsDNA. In AD samples, an additional dsDNA-stimulated protein, p40, was observed. In extracts prepared from sporadic AD individuals, synthetic dsDNA stimulated the phosphorylation of two additional proteins, with molecular weights of 73- and 37-kD, which were not found in familial AD or control samples. These results suggest that dsDNA-stimulated phosphoprotein changes may be used to distinguish between familial and sporadic forms of AD.
ISSN:1039-9712