Differential processing and secretion of Abeta peptides and sAPPalpha in human platelets is regulated by thrombin and prostaglandine 2.
Metabolic and functional studies of the amyloid precursor protein (APP) in platelets have advanced our understanding of Alzheimer's disease (AD). Here we report that human platelets contain Abeta peptides, process and secrete them constitutively. Platelets generate formerly unkown Abeta-species by differential processing of APP. Release of Abeta peptides were also increased by platelet activation with thrombin, indicating the existence of a regulated exocytotic pathway. We showed that Abeta-levels, Abeta-processing patterns and Abeta-release kinetics were regulated by thrombin. In controls, release of Abeta peptide species (Abeta 1-40/42 and 1-37/38/39/) continued for more than 4 h, while thrombin activated cells ceased secretion after 1 h at large. Treatment of platelets with prostaglandine 2 slowed this process down. Intracellular Abeta peptide concentrations decreased steadily until no peptides could be detected after 20 h (control) or after 4 h (thrombin) in cultured platelets.
Smirnov
A
A
Department of Psychiatry and Psychotherapy, University Hospital of Erlangen, Germany.
Trupp
A
A
Henkel
A W
AW
Bloch
E
E
Reulbach
U
U
Lewczuk
P
P
Riggert
J
J
Kornhuber
J
J
Wiltfang
J
J
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005089:Exocytosis / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D042541:Intracellular Space / Q000378:metabolism; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D003094:Collagen; D053829:Amyloid Precursor Protein Secretases; D013917:Thrombin; D015232:Dinoprostone