Tyrosine phosphorylation of human platelet plasma membrane Ca2+-ATPase in hypertension

Blankenship, Kristy A.; Dawson, C. B.; Aronoff, George R.; Dean, William L.

doi:10.1016/s0895-7061(99)80035-1

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…Blankenship et al. [22] showed that the increased platelet [Ca 2+ ] i observed in hypertension was correlated with increased tyrosine phosphorylation of PMCA, which also explains the earlier observation of decreased PMCA activity in hypertension [23]. Similarly, Rosado et al.…”

Section: Discussionmentioning

confidence: 89%

Effects of plasma membrane Ca2+‐ATPase tyrosine phosphorylation on human platelet function

Bozulic

Malik

Dean

2007

Journal of Thrombosis and Haemostasis

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Summary. Background: The plasma membrane Ca 2+ -ATPase (PMCA) plays an essential role in maintaining low intracellular Ca 2+ ([Ca 2+ ] i ) in resting platelets. Earlier studies demonstrated that platelet activation by thrombin results in tyrosine phosphorylation of PMCA, which inhibits pump activity. Objectives: The objective was to determine the functional consequences of PMCA tyrosine phosphorylation. Methods: A decapeptide including the tyrosine phosphorylation site of PMCA and a scrambled version were synthesized and introduced into human platelets using saponin. Fura-2 calcium monitoring and aggregometry were used to characterize the effects of inhibition of tyrosine phosphorylation. Results: Western blot analysis of immunoprecipitates showed that introduction of the inhibitory peptide decreased tyrosine phosphorylation of PMCA by nearly 60% in saponin-permeabilized, thrombin-treated platelets as compared with the scrambled control peptide. Concomitant with inhibition of PMCA tyrosine phosphorylation was a significant decrease in [Ca 2+ ] i during thrombin-mediated platelet activation. The functional consequence of reduced PMCA tyrosine phosphorylation and decreased [Ca 2+ ] i was a significant delay in the onset of thrombin-mediated platelet aggregation. Conclusions: The results demonstrate that PMCA tyrosine phosphorylation regulates [Ca 2+ ] i during platelet activation, which affects downstream events in the activation process. Moreover, PMCA tyrosine phosphorylation and resultant inhibition of PMCA activity produces a positive feedback loop mechanism by enhancing the increase in [Ca 2+ ] i accompanying platelet activation.

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Section: Discussionmentioning

confidence: 89%

Effects of plasma membrane Ca2+‐ATPase tyrosine phosphorylation on human platelet function

Bozulic

Malik

Dean

2007

Journal of Thrombosis and Haemostasis

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“…Although the control of hypertension has been established as an important factor in the primary and secondary prevention of stroke, the available clinical data suggest that the hypertension induced by a stroke can result in short‐term neurological improvement and is associated with favourable outcomes 33 . However, platelet Ca 2+ abnormalities have been reported in patients with hypertension and diabetes mellitus, in whom the modulation of plasma membrane Ca 2+ ‐ATPase (PMCA) activity and an increase in PMCA tyrosine phosphorylation may occur 34 . Thus, hypertension and diabetes mellitus may also contribute to the dysregulation of platelet Ca 2+ movement in acute stroke patients.…”

Section: Discussionmentioning

confidence: 99%

DYSREGULATION OF Ca²⁺ MOVEMENT IN PLATELETS FROM PATIENTS WITH ACUTE ISCHAEMIC STROKE

Tsai

Chang

et al. 2009

Clin Exp Pharma Physio

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1. Platelets play a pivotal role during acute ischaemic stroke. An increase in cytosolic Ca(2+) concentrations ([Ca(2+)](i)) triggers intracellular signal transduction, leading to platelet aggregation and thrombosis. In the present study, we examined the differences between platelets from acute ischaemic stroke patients and at-risk controls in terms of the increase in platelet [Ca(2+)](i). 2. Thirty-one patients with acute ischaemic stroke and 27 at-risk controls were enrolled in the present study. Platelet [Ca(2+)](i) was measured using the fluorescent dye fura-2 after stimulation with 100 micromol/L arachidonic acid (AA), 10 micromol/L ADP, 1 micromol/L platelet-activation factor (PAF) and 0.1 U/mL thrombin. 3. Basal [Ca(2+)](i) was higher in the stroke group compared with at-risk controls, irrespective of the presence or absence of extracellular Ca(2+). In Ca(2+)-containing medium, both PAF and ADP, but not AA and thrombin, significantly increased platelet [Ca(2+)](i) in the stroke group compared with the at-risk controls. However, in Ca(2+)-free medium, only PAF significantly increased platelet [Ca(2+)](i) in the stroke group compared with the at-risk controls. Basal [Ca(2+)](i) and PAF-induced platelet [Ca(2+)](i) increases were still higher in the stroke group at the subacute stage than in the at-risk controls. 4. The results of the present study provide direct evidence that Ca(2+) signalling in platelets from acute ischaemic stroke patients was altered in response to particular stimuli. The dysregulation of Ca(2+) movement in platelets may persist up to the subacute stage of ischaemic stroke.

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“…Circulating platelets are activated in response to a variety of physiological agonists, such as thrombin, that become available after the vascular injury. Platelet responsiveness might be altered by a number of pathological situations, including hypertension [33], myeloproliferative disorders [34] or diabetes mellitus [19, 32]. Oxidative stress has been shown to be involved in the development of abnormal signalling pathways leading to platelet hyperaggregability [35, 36].…”

Section: Discussionmentioning

confidence: 99%

Effect of homocysteine on calcium mobilization and platelet function in type 2 diabetes mellitus

Alexandru¹,

Jardín

Popov³

et al. 2008

J Cellular Molecular Medi

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Type 2 diabetes mellitus induces a characteristic platelet hyperactivity that might be due to several factors including oxidativ stress and abnormal intracellular Ca2+ homeostasis. Hyperhomocysteinaemia is considered a risk factor in the development of thrombosis although its effect on platelet function and the mechanisms involved are still poorly understood. Here we show tha homocysteine induce a concentration-dependent increase in endogenous production of reactive oxygen species (ROS), which was significantly greater in platelets from diabetic patients than in controls. Platelet treatment with homocysteine resulted in Ca2+ release from the dense tubular system and the acidic stores. Ca2+ mobilization-induced by homocysteine consisted in two components, an initial slow increase in intracellular free Ca + concentration ([Ca +]i) and a rapid and marked increase in [Ca2+]i, th second leading to the activation of platelet aggregation. As well as ROS generation, Ca2+ mobilization and platelet aggregation were significantly greater in platelets from diabetic donors than in controls, which indicate that platelets from diabetic donors are more sensitive to homocysteine. These findings, together with the hyperhomocysteinaemia reported in diabetic patients, strongly suggest that homocysteine might be considered a risk factor in the development of cardiovascular complications associated to type 2 diabetes mellitus.

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Tyrosine phosphorylation of human platelet plasma membrane Ca2+-ATPase in hypertension

Cited by 7 publications

References 14 publications

Effects of plasma membrane Ca2+‐ATPase tyrosine phosphorylation on human platelet function

Effects of plasma membrane Ca2+‐ATPase tyrosine phosphorylation on human platelet function

DYSREGULATION OF Ca²⁺ MOVEMENT IN PLATELETS FROM PATIENTS WITH ACUTE ISCHAEMIC STROKE

Effect of homocysteine on calcium mobilization and platelet function in type 2 diabetes mellitus

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Tyrosine phosphorylation of human platelet plasma membrane Ca2+-ATPase in hypertension

Cited by 7 publications

References 14 publications

Effects of plasma membrane Ca2+‐ATPase tyrosine phosphorylation on human platelet function

Effects of plasma membrane Ca2+‐ATPase tyrosine phosphorylation on human platelet function

DYSREGULATION OF Ca2+ MOVEMENT IN PLATELETS FROM PATIENTS WITH ACUTE ISCHAEMIC STROKE

Effect of homocysteine on calcium mobilization and platelet function in type 2 diabetes mellitus

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DYSREGULATION OF Ca²⁺ MOVEMENT IN PLATELETS FROM PATIENTS WITH ACUTE ISCHAEMIC STROKE