Platelets and DAMI megakaryocytes possess beta-secretase-like activity
| Autor: | Derek C.L. Marshall, Heidi J. Long, Heather Tibbles, Theresa A. Davies, Ryan Hastey, Elizabeth R. Simons, Kimberly Otto, Sally J. Smith, Andrea M. Billingslea, Richard E. Fine, Carmela R. Abraham, Robin J. Johnson |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Blood Platelets
Proteases Pathology and Forensic Medicine Substrate Specificity chemistry.chemical_compound Amyloid beta-Protein Precursor Naphthalenesulfonates Alzheimer Disease AEBSF P aminobenzoate Endopeptidases Amyloid precursor protein Tumor Cells Cultured Aspartic Acid Endopeptidases Humans Enzyme Inhibitors Serine protease Metalloproteinase biology Serine Endopeptidases Thrombin Antibodies Monoclonal Membrane Proteins Metalloendopeptidases General Medicine Biochemistry Glycoprotein Ib chemistry Cell culture biology.protein Amyloid Precursor Protein Secretases Peptides Megakaryocytes Oligopeptides |
| Zdroj: | The Journal of laboratory and clinical medicine. 133(5) |
| ISSN: | 0022-2143 |
| Popis: | We report here the discovery of two novel human platelet and megakaryocytic DAMI cell enzymes that have β-secretase-like activity. These activities could potentially effect cleavage of the amyloid precursor protein (APP) at the β-amyloid peptide N-terminus, by an EC 3.4.24.15-like metalloprotease, and the N terminus-1 position, by a serine protease. Thus both enzymes may generate the amyloidogenic β-peptide. Studies of intact and Triton X-100-lysed DAMI cells, as well as intact versus subcellular fractions of platelets, demonstrate the presence of these proteolytic activities. The resting platelet has (1) a surface serine protease, demonstrated by its ability to cleave a β-secretase substrate and by its inhibitor sensitivity; and (2) a metalloprotease, recognized by an antibody to EC 3.4.24.15, which resides intracellularly in the α-granule membrane, is translocated to the surface on activation, and shows β-secretase-like activity by cleaving the same substrate. This metalloprotease can also cleave recombinant APP to a potentially amyloidogenic fragment. Surface metalloprotease was identified in DAMI cells by flow cytometry and Western blotting with a specific anti-EC 3.4.24.15 monoclonal antibody, while activity was identified by using two β-secretase substrates. This article is the first to document two previously unknown endoproteinases with β-secretase-like activity in platelets and DAMI cells. These proteases are capable of effecting cleavage of APP and could therefore contribute to Aβ deposition in the cerebrovasculature. (J Lab Clin Med 1999;133:507-15) |
| Databáze: | OpenAIRE |
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