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 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.
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Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595.
Wu
J M
JM
D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D008970:Molecular Weight; D009698:Nucleoproteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011067:Poly dA-dT / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D012867:Skin
D000911:Antibodies, Monoclonal; D009698:Nucleoproteins; D010750:Phosphoproteins; D011067:Poly dA-dT; D004247:DNA; D011494:Protein Kinases