title: A human brain proteolytic activity capable of cleaving natural beta-amyloid precursor protein is affected by its substrate glycoconjugates.
abstract: Human brain proteins were partially purified by using arginine-Sepharose 4B affinity chromatography, which traps proteins having an affinity to certain groups of arginine residue, such as serine proteases and zymogens. Bound proteins were analyzed for binding and cleavage related to the brain beta-amyloid precursor protein (APP). They were then further separated and isolated using a preparative gel system having a liquid-phase collection apparatus, using a non-denaturing gel system. Each fractionated protein was also analyzed for the above activity using natural APP. Among these, we found several fractions that bind preferentially to APP treated with chondroitinase ABC but not to intact APP, and that also generate particular beta-amyloid containing C-terminal peptides of APP via proteolysis. Our results suggest that sulfated glycoconjugates attached to APP play a role in the substrate specificity of APP for proteases, and also that the nature of natural APP processing mechanisms in vivo is very complex.
authors.affiliation: Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsumoto
authors.forename: R
authors.initials: R
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Enomoto
authors.forename: K
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry / Q000502:physiology; D002458:Cell Fractionation; D002846:Chromatography, Affinity; D010450:Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D006001:Glycoconjugates / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013379:Substrate Specificity; D013431:Sulfates / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D006001:Glycoconjugates; D013431:Sulfates; D010450:Endopeptidases