Zinc-dependent activation of the plasma kinin-forming cascade by aggregated beta amyloid protein
Copyright 1999 Academic Press.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 90(1999), 1 vom: 27. Jan., Seite 89-99 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
1999
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Amyloid beta-Peptides Kininogens Kinins Peptide Fragments amyloid beta-protein (1-38) amyloid beta-protein (1-40) amyloid beta-protein (1-42) Factor XII 9001-30-3 mehr... |
| Zusammenfassung: | Copyright 1999 Academic Press. Beta Amyloid proteins (Abeta) of 38, 40, and 42 amino acids long were assessed for their ability to activate the plasma kinin-forming cascade in vitro. Incubation with a mixture of Factor XII (Hageman Factor), prekallikrein, and high-molecular-weight kininogen (HK) led to conversion of prekallikrein to kallikrein that was dependent on zinc ion. No activation occurred if Factor XII was omitted. There was rapid generation of bradykinin equal to the molar HK input indicating complete cleavage. Incubation of aggregated Abeta with diluted human plasma also led to prekallikrein activation and HK cleavage. Activation of the cascade by Abeta (1-38) was dependent upon its preincubation time in buffer, suggesting that aggregation of Abeta is required, and studies with Abeta (1-40) revealed time-dependent aggregation by microscopy and augmented zinc-dependent binding of both Factor XII and HK to aggregated Abeta. These data demonstrate that aggregated Abeta can bind and activate proenzymes of the plasma kinin-forming cascade in a zinc-dependent reaction to release bradykinin and is of sufficient potency to do so at physiologic concentrations of each protein and in the presence of naturally occurring protease inhibitors |
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| Beschreibung: | Date Completed 05.03.1999 Date Revised 21.03.2022 published: Print Citation Status MEDLINE |
| ISSN: | 1521-7035 |