Sonkar 2014 FASEB J: Difference between revisions
(Created page with "{{Publication |title=Sonkar VK, Kulkarni PP, Dash D (2014) Amyloid � peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization. FASEB ...") |
No edit summary |
||
| Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=Sonkar VK, Kulkarni PP, Dash D (2014) Amyloid | |title=Sonkar VK, Kulkarni PP, Dash D (2014) Amyloid beta peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization. FASEB J [Epub ahead of print]. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/24421399 PMID:24421399] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/24421399 PMID:24421399] | ||
|authors=Sonkar VK, Kulkarni PP, Dash D | |authors=Sonkar VK, Kulkarni PP, Dash D | ||
| Line 6: | Line 6: | ||
|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=platelet adhesion | |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 | |area=Respiration, mt-Medicine | ||
|organism=Human, Mouse | |||
|tissues=Blood cells | |||
|model cell lines=Platelet | |||
|preparations=Intact cells | |||
|couplingstates=LEAK, ROUTINE | |||
|substratestates=ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=Labels, [Epub ahead of print] | |additional=Labels, [Epub ahead of print] | ||
}} | }} | ||
Revision as of 18:05, 28 January 2014
| Sonkar VK, Kulkarni PP, Dash D (2014) Amyloid beta peptide stimulates platelet activation through RhoA-dependent modulation of actomyosin organization. FASEB J [Epub ahead of print]. |
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
Organism: Human, Mouse
Tissue;cell: Blood cells
Preparation: Intact cells
Coupling state: LEAK, ROUTINE
HRR: Oxygraph-2k
Labels, [Epub ahead of print]
