Platelet-derived microvesicles activate human platelets via intracellular calcium mediated reactive oxygen species release

Yadav, Pooja; Beura, Samir Kumar; Panigrahi, Abhishek; Bhardwaj, Taniya; Giri, Rajanish; Singh, Sarita

doi:10.1016/j.bcmd.2022.102701

Cited by 10 publications

(10 citation statements)

References 34 publications

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“…Apart from that, our own findings showed that PMVs activates platelet that is characterized by the expression of high affinity (open conformation) integrin αIIbβ3 and also induces P‐selectin expression in platelets. Our finding depicts that PMVs trigger platelet activation by stimulating an elevation in ROS production, which was found to be regulated by the calcium‐dependent PLC‐IP 3 axis (Yadav et al, 2023). Additionally, our studies demonstrated that PMVs potentiate thrombin‐induced platelet aggregation and clot retraction, as depicted in the Supporting Information: Figures S1 and S2.…”

Section: Discussionsupporting

confidence: 52%

“…In our previous study, we found that PMVs activate platelets by increasing reactive oxygen species (ROS) production through the activation of NOX enzyme. This ROS generation is regulated by the calcium‐dependent PLC‐IP 3 axis, but the precise mechanism remains unclear and requires further investigation (Yadav et al, 2023). This study investigates the effect of PMVs on intracellular calcium oscillations.…”

Section: Resultsmentioning

confidence: 99%

“…Despite The preparation of PMVs (platelet-derived microparticles) was carried out as per our previously reported research (Yadav et al, 2023). In brief, PMVs were obtained from washed platelets by treating them with calcium ionophore.…”

Section: Cell Ell B Biology Iology I International Nternationalmentioning

confidence: 99%

“…This ROS generation is regulated by the calcium-dependent PLC-IP 3 axis, but the precise mechanism remains unclear and requires further investigation (Yadav et al, 2023). This study investigates the effect of PMVs on intracellular calcium oscillations.…”

Section: Pmvs Induce Free Intracellular Calcium In Plateletsmentioning

confidence: 99%

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Platelet‐derived microvesicles induce intracellular calcium mobilization in human platelets

Yadav,

Panigrahi,

Beura

et al. 2023

Cell Biology International

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Platelet‐derived microvesicles (PMVs) represent a significant proportion of microvesicles in circulation and have been linked to various pathophysiological complications. Recent research suggests that PMVs carry significant amounts of cargo that can affect cellular functions by influencing calcium oscillations in target cells. As calcium is involved in multiple cellular processes, including hemostasis and thrombosis, this study aimed to investigate the impact of PMVs on platelet calcium mobilization. The study found that PMVs increase platelet intracellular calcium levels via both intracellular storage and extracellular space in a dose‐dependent manner. The study highlighted the critical role of the dense tubular system, acidic vacuoles, mitochondrial stores, and store‐operated calcium entry (SOCE) in PMV‐mediated calcium release in human platelets. Moreover, the study revealed that PMV‐induced calcium rise in platelets does not occur via sarcoendoplasmic reticulum calcium ATPase, and extracellular calcium addition further increases the calcium level in platelets, demonstrating the involvement of SOCE. These findings provide insights into the platelet stimulation signaling mechanisms and contributes to our understanding of platelet and cell behavior when exposed to PMV‐rich environments.

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Section: Discussionsupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Cell Ell B Biology Iology I International Nternationalmentioning

confidence: 99%

Section: Pmvs Induce Free Intracellular Calcium In Plateletsmentioning

confidence: 99%

See 2 more Smart Citations

Platelet‐derived microvesicles induce intracellular calcium mobilization in human platelets

Yadav,

Panigrahi,

Beura

et al. 2023

Cell Biology International

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“…Subsequently, the platelets were exposed to 100 μM ROT for 20 min. In separate experiments, the platelets were also treated with specific inhibitors, including 0.5 M NAC (total ROS scavenger), 100 µM APO (NADPH oxidase [NOX] inhibitor and radical scavenger), 30 µM BAPTA-AM (cytosolic Ca 2+ chelator), 100 µM 2-APB (inositol 1,3,5-triphosphate receptor [IP 3 R] blocker), [25,28] and 10 µM CHE (protein kinase C [PKC] inhibitor) [29] for another 20 min at 37°C. The emitted fluorescence from DCF was quantified using a multimode microplate reader (Tecan Spark TM ) with excitation at 485 nm and emission at 535 nm.…”

Section: Study Of Platelet Ros Productionmentioning

confidence: 99%

Investigating the role of rotenone on human blood platelets: Molecular insights into abnormal platelet functions in Parkinson's disease

Beura,

Sahoo,

Yadav

et al. 2024

J Biochem & Molecular Tox

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Parkinson's disease (PD) is a predominant neuromotor disorder characterized by the selective death of dopaminergic neurons in the midbrain. The majority of PD cases are sporadic or idiopathic, with environmental toxins and pollutants potentially contributing to its development or exacerbation. However, clinical PD patients are often associated with a reduced stroke frequency, where circulating blood platelets are indispensable. Although platelet structural impairment is evident in PD, the platelet functional alterations and their underlying molecular mechanisms are still obscure. Therefore, we investigated rotenone (ROT), an environmental neurotoxin that selectively destroys dopaminergic neurons mimicking PD, on human blood platelets to explore its impact on platelet functions, thus replicating PD conditions in vitro. Our study deciphered that ROT decreased thrombin‐induced platelet functions, including adhesion, activation, secretion, and aggregation in human blood platelets. As ROT is primarily responsible for generating intracellular reactive oxygen species (ROS), and ROS is a key player regulating the platelet functional parameters, we went on to check the effect of ROT on platelet ROS production. In our investigation, it became evident that ROT treatment resulted in the stimulation of ROS production in human blood platelets. Additionally, we discovered that ROT induced ROS production by augmenting Ca2+ mobilization from inositol 1,4,5‐trisphosphate receptor. Apart from this, the treatment of ROT triggers protein kinase C associated NADPH oxidase‐mediated ROS production in platelets. In summary, this research, for the first time, highlights ROT‐induced abnormal platelet functions and may provide a mechanistic insight into the altered platelet activities observed in PD patients.

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Lysophosphatidylcholine induces oxidative stress and calcium‐mediated cell death in human blood platelets

Yadav,

Beura,

Panigrahi

et al. 2024

Cell Biology International

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Platelets are essential component of circulation that plays a major role in hemostasis and thrombosis. During activation and its demise, platelets release platelet‐derived microvesicles, with lysophosphatidylcholine (LPC) being a prominent component in their lipid composition. LPC, an oxidized low‐density lipoprotein, is involved in cellular metabolism, but its higher level is implicated in pathologies like atherosclerosis, diabetes, and inflammatory disorders. Despite this, its impact on platelet function remains relatively unexplored. To address this, we studied LPC's effects on washed human platelets. A multimode plate reader was employed to measure reactive oxygen species and intracellular calcium using H2DCF‐DA and Fluo‐4‐AM, respectively. Flow cytometry was utilized to measure phosphatidylserine expression, mitochondrial membrane potential (ΔΨm), and mitochondrial permeability transition pore (mPTP) formation using FITC‐Annexin V, JC‐1, and CoCl2/calcein‐AM, respectively. Additionally, platelet morphology and its ultrastructure were observed via phase contrast and electron microscopy. Sonoclot and light transmission aggregometry were employed to examine fibrin formation and platelet aggregation, respectively. The findings demonstrate that LPC induced oxidative stress and increased intracellular calcium in platelets, resulting in increased phosphatidylserine expression and reduced ΔΨm. LPC triggered caspase‐independent platelet death and mPTP opening via cytosolic and mitochondrial calcium, along with microvesiculation and reduced platelet counts. LPC increased the platelet's size, adopting a balloon‐shaped morphology, causing membrane fragmentation and releasing its cellular contents, while inducing a pro‐coagulant phenotype with increased fibrin formation and reduced integrin αIIbβ3 activation. Conclusively, this study reveals LPC‐induced oxidative stress and calcium‐mediated platelet death, necrotic in nature with pro‐coagulant properties, potentially impacting inflammation and repair mechanisms during vascular injury.

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Platelet-derived microvesicles activate human platelets via intracellular calcium mediated reactive oxygen species release

Cited by 10 publications

References 34 publications

Platelet‐derived microvesicles induce intracellular calcium mobilization in human platelets

Platelet‐derived microvesicles induce intracellular calcium mobilization in human platelets

Investigating the role of rotenone on human blood platelets: Molecular insights into abnormal platelet functions in Parkinson's disease

Lysophosphatidylcholine induces oxidative stress and calcium‐mediated cell death in human blood platelets

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