Sonkar 2014 FASEB J
|Sonkar VK, Kulkarni PP, Dash D (2014) Amyloid beta peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization. FASEB J 28:1819-29.|
Abstract: Platelets contribute to 95% of circulating amyloid precursor protein in the body and have widely been employed as a "peripheral" model of neurons in Alzheimer's disease. We sought to analyze the effects of amyloid β (Aβ) on platelets and to understand the underlying molecular mechanism. The Aβ active fragment containing amino acid sequence 25-35 (Aβ25-35; 10-20 μM) was found to induce strong aggregation of human platelets, granule release, and integrin activation, similar to that elicited by physiological agonists. Platelets exposed to Aβ25-35 retracted fibrin clot and displayed augmented adhesion to collagen under arterial shear, reflective of a switch to prothrombotic phenotype. Exposure of platelets to Aβ peptide (20 μM) 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). Aβ25-35-induced platelet aggregation and clot retraction were also significantly attenuated by Y27632. Consistent with these findings, Aβ25-35 elicited a significant rise in the level of RhoA-GTP in platelets. Platelets pretreated with reverse-sequenced Aβ fragment (Aβ35-25) and untreated resting platelets served as controls. We conclude that Aβ induces cellular activation through RhoA-dependent modulation of actomyosin, and hence, RhoA could be a potential therapeutic target in Alzheimer's disease and cerebral amyloid angiopathy.-Sonkar, V. K., Kulkarni, P. P., Dash, D. Amyloid β peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization.
• Keywords: Platelet adhesion, Clot retraction, Mitochondrial respiration, Myosin light chain, Thromboembolism
• O2k-Network Lab: IN Varanasi Dash D
Labels: MiParea: Respiration, mt-Medicine
Organism: Human, Mouse Tissue;cell: Blood cells, Platelet Preparation: Intact cells
Coupling state: LEAK, ROUTINE Pathway: ROX HRR: Oxygraph-2k