Amyloid β peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization

Sonkar, Vijay K. ; Kulkarni, Paresh P. ; Dash, Debabrata (2014) Amyloid β peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization The FASEB Journal, 28 (4). pp. 1819-1829. ISSN 0892-6638

Full text not available from this repository.

Official URL: http://www.fasebj.org/content/28/4/1819.abstract

Related URL: http://dx.doi.org/10.1096/fj.13-243691

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.

Item Type:Article
Source:Copyright of this article belongs to Federation of American Societies for Experimental Biology.
Keywords:Platelet Adhesion; Clot Retraction; Mitochondrial Respiration; Myosin Light Chain; Thromboembolism
ID Code:100916
Deposited On:04 Feb 2017 17:26
Last Modified:04 Feb 2017 17:26

Repository Staff Only: item control page