Affordable Access

Publisher Website

Platelets and DAMI megakaryocytes possess β-secretase-like activity

Mosby, Inc.
DOI: 10.1016/s0022-2143(99)90028-8
  • Biology


Abstract 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 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, 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 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.

There are no comments yet on this publication. Be the first to share your thoughts.


Seen <100 times