title: Purification of a trypsin-type protease from human umbilical vein endothelial cells which is highly sensitive to the Kunitz inhibitor domain peptide of Alzheimer's disease amyloid protein precursor.
abstract: A trypsin-type protease was purified to enzymatic homogeneity from human umbilical vein endothelial cells by sequential affinity chromatographies. The enzyme specifically hydrolyzed dibasic substrates with leucine at the P3 positions, but scarcely hydrolyzed the other substrates tested. The enzyme was strongly inhibited by the Kunitz inhibitor domain peptide of Alzheimer's disease amyloid protein precursor (Ki value, 0.35 nM) and by the microbial inhibitors leupeptin and anti-pain. These results, together with a previous finding of a significant increase in the expression of Alzheimer's amyloid protein precursors (beta APPs) with the Kunitz inhibitor domain in Alzheimer's disease, suggest that the activity of the trypsin-type protease is suppressed by an increase of beta APPs with inhibitor activity in Alzheimer's disease, resulting in aberrant intracellular protein catabolism including degradation of beta APPs and beta-protein deposition.
authors.affiliation: Division of Enzyme Chemistry, University of Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kido
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: H
authors.initials: H
authors.lastname: Wakabayashi
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Takenaka
authors.forename: M
authors.initials: M
authors.lastname: Okada
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D010446:Peptide Fragments / Q000494:pharmacology; D013379:Substrate Specificity; D014357:Trypsin / Q000302:isolation & purification*; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology
chemical_list: D016564:Amyloid beta-Protein Precursor; D009842:Oligopeptides; D010446:Peptide Fragments; D014360:Trypsin Inhibitor, Kunitz Soybean; D014357:Trypsin