Carboxy-terminal truncation of long-tailed amyloid beta-peptide is inhibited by serine protease inhibitor and peptide aldehyde.
The 42/43-residue amyloid beta-peptide (Abeta) is widely believed to play a major role in Alzheimer's disease. The present study shows that the rat brain contains a carboxypeptidase that efficiently deletes three amino acids from Abeta1-43. The carboxypeptidase activity in the brain was completely inhibited by 1 mM phenylmethylsulfonyl fluoride, suggesting the protease is a serine carboxypeptidase. The carboxy-terminal truncation of Abeta1-43 was moderately inhibited by carbobenzoxy-Leu-leucinal, carbobenzoxy-Leu-Leu-leucinal, and carbobenzoxy-Leu-Leu-norvalinal, and weakly by antipain. The present data suggest that the serine carboxypeptidase contributes to the generation of short-tailed Abeta peptides and is important in the intracellular clearance of Abeta1-42/43 in brains.
Hamazaki
H
H
Department of Biology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
D000596:Amino Acids / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000976:Antipain / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002729:Chloromercuribenzoates / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D010436:Pepstatins / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D020245:p-Chloromercuribenzoic Acid
D000596:Amino Acids; D016229:Amyloid beta-Peptides; D002729:Chloromercuribenzoates; D007976:Leupeptins; D010436:Pepstatins; D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; C098994:amyloid beta-protein (1-43); C014195:Streptomyces pepsin inhibitor; D000976:Antipain; D010664:Phenylmethylsulfonyl Fluoride; D020245:p-Chloromercuribenzoic Acid; D004492:Edetic Acid; D002268:Carboxypeptidases; C032854:leupeptin; C031375:pepstatin