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Effects of staurosporine, U-73122, wortmannin, 4-hydroxynonenal and sodium azide upon the release of secreted β-amyloid precursor protein from human platelets in response to thrombin stimulation

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Abstract

In the present study, the release of secreted β-amyloid precursor protein (AβPPs) in response to thrombin stimulation in platelets has been investigated. Incubation of platelets with thrombin produced a concentration-dependent release of AβPPs with a concomitant reduction in the AβPP 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 AβPPs from human platelets via an activation of a phospholipase C-independent pathway. Thrombin-stimulated AβPPs 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.

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  1. Department of Pharmacology and Clinical Neuroscience, Umeå University, SE 901 87, Umeå, Sweden

    Henrietta L.M. Hedin, Lisa Nilsson & Christopher J. Fowler

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  1. Henrietta L.M. Hedin
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  2. Lisa Nilsson
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Hedin, H.L., Nilsson, L. & Fowler, C.J. Effects of staurosporine, U-73122, wortmannin, 4-hydroxynonenal and sodium azide upon the release of secreted β-amyloid precursor protein from human platelets in response to thrombin stimulation. Mol Cell Biochem 219, 145–152 (2001). https://doi.org/10.1023/A:1010863415115

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