Alzheimer's disease brain-derived ubiquitin has amyloid-enhancing factor activity: behavior of ubiquitin during accelerated amyloidogenesis.
Amyloid-enhancing factor (AEF) is believed to be a crucial common pathogenetic link in diverse forms of human amyloidosis. Passive transfer of crude AEF is known to trigger accelerated splenic amyloid deposition in mice. We have recently identified AEF activity in ubiquitin isolated from murine amyloidotic tissues. Using similar techniques we have purified ubiquitin, from crude Alzheimer's disease (AD) brain extracts, to apparent homogeneity. Based on the partial amino acid sequence homology, immunochemical and pathophysiological criteria, the approximately 5.5-kDa AD-derived protein was identified as ubiquitin (AD-ubiquitin) with AEF activity. Ten to twenty micrograms of this protein per mouse, with or without CaCl2, in conjunction with four subcutaneous injections of 0.5 ml of 1% aqueous AgNO3, induced accelerated splenic amyloid deposition. By immunohistochemistry, using anti-mouse AA amyloid antibody, the AD-ubiquitin-induced amyloid was identified as AA type. With anti-bovine ubiquitin antibody, using similar spleen sections as above, ubiquitin was found to co-deposit with AA amyloid in the splenic perifollicular areas. These results strongly suggest that ubiquitin may be involved in the pathogenesis of amyloidosis.
Alizadeh-Khiavi
K
K
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Normand
J
J
Chronopoulos
S
S
Ali-Khan
Z
Z
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000473:pathology; D002122:Calcium Chloride / Q000494:pharmacology; D003224:Congo Red; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D014452:Ubiquitins / Q000032:analysis / Q000378:metabolism*
D006023:Glycoproteins; D000685:Serum Amyloid A Protein; D014452:Ubiquitins; C046748:amyloid enhancing factor; D003224:Congo Red; D002122:Calcium Chloride