Sonkar 2014 FASEB J: Difference between revisions
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|journal=FASEB J | |journal=FASEB J | ||
|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. | |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= | |keywords=Platelet adhesion, Clot retraction, Mitochondrial respiration, Myosin light chain, Thromboembolism | ||
|mipnetlab=IN Varanasi Dash D | |mipnetlab=IN Varanasi Dash D | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, mt-Medicine | |area=Respiration, mt-Medicine | ||
|diseases=Alzheimer's | |||
|organism=Human, Mouse | |organism=Human, Mouse | ||
|tissues=Blood cells | |tissues=Blood cells, Platelet | ||
|preparations=Intact cells | |preparations=Intact cells | ||
|couplingstates=LEAK, ROUTINE | |couplingstates=LEAK, ROUTINE | ||
| | |pathways=ROX | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional= | |additional=MitoEAGLE blood cells data, | ||
}} | }} |
Latest revision as of 13:42, 2 March 2020
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. |
Sonkar VK, Kulkarni PP, Dash D (2014) FASEB J
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
Pathology: Alzheimer's
Organism: Human, Mouse Tissue;cell: Blood cells, Platelet Preparation: Intact cells
Coupling state: LEAK, ROUTINE
Pathway: ROX
HRR: Oxygraph-2k
MitoEAGLE blood cells data