Mallick 2015 Cell Calcium: Difference between revisions
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|abstract=Prion diseases are neurodegenerative disorders where infectious prion proteins (PrP) accumulate in brainleading to aggregation of amyloid fibrils and neuronal cell death. The amino acid sequence 106β126 fromprion proteins, PrP(106β126), is highly amyloidogenic and implicated in prion-induced pathologies. AsPrP is known to be expressed in blood following leakage from brain tissue, we sought to investigate its biological effects on human platelets, which have been widely employed as βperipheralβ model for neurons. Our findings suggested that, PrP(106β126) (20 Β΅M) induced dramatic 30-fold rise in intracellular calcium (from 105 Β± 30 to 3425 Β± 525 nM) in platelets, which was attributable to influx from extracellular fluid with comparatively less contribution from intracellular stores. Calcium mobilization was associated with 8β10-fold stimulation in the activity of thiol protease calpain that led to partial cleavage of cytoskeleton-associated protein talin and extensive shedding of microparticles from platelets, thus transforming platelets to βactivatedβ phenotype. Both proteolysis of talin and microparticle release were precluded by calpeptin, a specific inhibitor of calpain. As microparticles are endowed with phosphatidylserine-enriched surface and hence are pro-coagulant in nature, exposure to prion favored a thrombogenic state in the organism. | |abstract=Prion diseases are neurodegenerative disorders where infectious prion proteins (PrP) accumulate in brainleading to aggregation of amyloid fibrils and neuronal cell death. The amino acid sequence 106β126 fromprion proteins, PrP(106β126), is highly amyloidogenic and implicated in prion-induced pathologies. AsPrP is known to be expressed in blood following leakage from brain tissue, we sought to investigate its biological effects on human platelets, which have been widely employed as βperipheralβ model for neurons. Our findings suggested that, PrP(106β126) (20 Β΅M) induced dramatic 30-fold rise in intracellular calcium (from 105 Β± 30 to 3425 Β± 525 nM) in platelets, which was attributable to influx from extracellular fluid with comparatively less contribution from intracellular stores. Calcium mobilization was associated with 8β10-fold stimulation in the activity of thiol protease calpain that led to partial cleavage of cytoskeleton-associated protein talin and extensive shedding of microparticles from platelets, thus transforming platelets to βactivatedβ phenotype. Both proteolysis of talin and microparticle release were precluded by calpeptin, a specific inhibitor of calpain. As microparticles are endowed with phosphatidylserine-enriched surface and hence are pro-coagulant in nature, exposure to prion favored a thrombogenic state in the organism. | ||
|keywords=Prion, Platelets, Intracellular calcium, Calpain, Microparticles | |keywords=Prion, Platelets, Intracellular calcium, Calpain, Microparticles | ||
|mipnetlab=US NC Durham Li | |mipnetlab=US NC Durham Li PA, IN Varanasi Dash D, IN Haldia Chakrabarti S | ||
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Revision as of 11:21, 10 November 2015
Mallick RL, Kumari S, Singh N, Sonkar VK, Dash D (2015) Prion protein fragment (106-126) induces prothrombotic state by raising platelet intracellular calcium and microparticle release. Cell Calcium 57:300-11. |
Mallick RL, Kumari S, Singh N, Sonkar VK, Dash D (2015) Cell Calcium
Abstract: Prion diseases are neurodegenerative disorders where infectious prion proteins (PrP) accumulate in brainleading to aggregation of amyloid fibrils and neuronal cell death. The amino acid sequence 106β126 fromprion proteins, PrP(106β126), is highly amyloidogenic and implicated in prion-induced pathologies. AsPrP is known to be expressed in blood following leakage from brain tissue, we sought to investigate its biological effects on human platelets, which have been widely employed as βperipheralβ model for neurons. Our findings suggested that, PrP(106β126) (20 Β΅M) induced dramatic 30-fold rise in intracellular calcium (from 105 Β± 30 to 3425 Β± 525 nM) in platelets, which was attributable to influx from extracellular fluid with comparatively less contribution from intracellular stores. Calcium mobilization was associated with 8β10-fold stimulation in the activity of thiol protease calpain that led to partial cleavage of cytoskeleton-associated protein talin and extensive shedding of microparticles from platelets, thus transforming platelets to βactivatedβ phenotype. Both proteolysis of talin and microparticle release were precluded by calpeptin, a specific inhibitor of calpain. As microparticles are endowed with phosphatidylserine-enriched surface and hence are pro-coagulant in nature, exposure to prion favored a thrombogenic state in the organism. β’ Keywords: Prion, Platelets, Intracellular calcium, Calpain, Microparticles
β’ O2k-Network Lab: US NC Durham Li PA, IN Varanasi Dash D, IN Haldia Chakrabarti S
Labels: MiParea: Respiration
Pathology: Other
Organism: Human Tissue;cell: Blood cells
Coupling state: LEAK, ROUTINE
HRR: Oxygraph-2k
Labels