科研之友
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摘要
Platelets contribute to 95% of circulating amyloid precursor protein in the body and have widely been employed as a %26quot;peripheral%26quot; model of neurons in Alzheimer%26apos;s disease. We sought to analyze the effects of amyloid beta (A beta) on platelets and to understand the underlying molecular mechanism. The A beta active fragment containing amino acid sequence 25-35 (A beta(25-35); 10-20 mu M) was found to induce strong aggregation of human platelets, granule release, and integrin activation, similar to that elicited by physiological agonists. Platelets exposed to A beta(25-35) retracted fibrin clot and displayed augmented adhesion to collagen under arterial shear, reflective of a switch to prothrombotic phenotype. Exposure of platelets to A beta peptide (20 mu M) resulted in a 4.2- and 2.3-fold increase in phosphorylation of myosin light chain (MLC) and MLC phosphatase, respectively, which was reversed by Y27632, an inhibitor of Rho-associated coiled-coil protein kinase (ROCK). A beta(25-35)-induced platelet aggregation and clot retraction were also significantly attenuated by Y27632. Consistent with these findings, A beta(25-35) elicited a significant rise in the level of RhoA-GTP in platelets. Platelets pretreated with reverse-sequenced A beta fragment (A beta(35-25)) and untreated resting platelets served as controls. We conclude that A beta induces cellular activation through RhoA-dependent modulation of actomyosin, and hence, RhoA could be a potential therapeutic target in Alzheimer%26apos;s disease and cerebral amyloid angiopathy.-Sonkar, V. K., Kulkarni, P. P., Dash, D. Amyloid beta peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization.
- 出版日期2014-4
- 单位河北医科大学
