Effects of staurosporine, U-73122, wortmannin, 4-hydroxynonenal and sodium azide upon the release of secreted beta-amyloid precursor protein from human platelets in response to thrombin stimulation.
In the present study, the release of secreted beta-amyloid precursor protein (AbetaPPs) in response to thrombin stimulation in platelets has been investigated. Incubation of platelets with thrombin produced a concentration-dependent release of AbetaPPs with a concomitant reduction in the AbetaPP remaining in the lysates. The response to thrombin was not affected by pretreatment for 15 min with the phospholipase C inhibitor U-73122, with the protein kinase C inhibitor staurosporine, or with hydrogen peroxide (which at the concentrations used affects the phosphoinositide signalling system in human platelets). In contrast, pretreatment with wortmannin and sodium azide reduced the responses to thrombin. These data would suggest that thrombin may cause the release of AbetaPPs from human platelets via an activation of a phospholipase C-independent pathway. Thrombin-stimulated AbetaPPs release was also reduced by 4-hydroxynonenal. This finding, if it is a phenomenon also found for CNS cells, could be of relevance to the pathogenesis of Alzheimer's disease, given that an accumulation of 4-hydroxynonenal is found in this disease.
Hedin
H L
HL
Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden.
Nilsson
L
L
Fowler
C J
CJ
D000447:Aldehydes / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D019810:Sodium Azide / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D000077191:Wortmannin
D000447:Aldehydes; D016564:Amyloid beta-Protein Precursor; D000730:Androstadienes; D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019810:Sodium Azide; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D010738:Type C Phospholipases; D013917:Thrombin; D019311:Staurosporine; C027576:4-hydroxy-2-nonenal; D000077191:Wortmannin