What question did this study set out to answer?

Determine the relative contributions of oxidative phosphorylation and glycolysis during human platelet activation and characterize the signaling pathway behind thrombin-induced metabolic stimulation.

August 17, 2017PLoS ONEOpen Access

Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

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Population

Human platelets

Comparison

Activation by thrombin and other agonists vs Non-activated platelets

Design

Preclinical

Authors

NPNorma Corona de la PeñaMexican Social Security Institute MGManuel Gutiérrez‐AguilarUniversidad Autónoma de la Ciudad de México IHIleana Hernández‐ReséndizUniversity Hospital Regensburg

Discussion

Member takes

Implication

Thrombin may preferentially engage mitochondrial ATP production via GPIb signaling; leaves open whether OxPhos targeting alters platelet function in vivo.

Key Points

Determine the relative contributions of oxidative phosphorylation and glycolysis during human platelet activation and characterize the signaling pathway behind thrombin-induced metabolic stimulation.
Measured glycolytic flux, oxidative phosphorylation (OxPhos), and mitochondrial transmembrane potential in human platelets exposed to multiple agonists including thrombin, Trap-6, collagen, and ADP.
Assessed signaling mechanisms involved in thrombin-driven mitochondrial activation using selective inhibitors of PI3K/Akt, glycoprotein Ib (GPIb), calcium mobilization, and tyrosine phosphorylation.
Diverse agonists elevated glycolytic flux 3- to 38-fold, whereas only thrombin stimulated OxPhos (33-fold) and mitochondrial transmembrane potential (88%), establishing OxPhos as thrombin's primary ATP contributor.
Pharmacological inhibition of PI3K/Akt (wortmannin, LY294002), GPIb (ristocetin, heparin), calcium mobilization (resveratrol, ATP), and tyrosine phosphorylation (PP1) suppressed thrombin-mediated activation.

Structured PICO

Population

Human platelets

Intervention

Activation by thrombin and other agonists (Trap-6, arachidonic acid, collagen, A23187, epinephrine, ADP)

Comparator

Non-activated platelets

Outcome

Energy metabolism pathways (glycolytic flux and oxidative phosphorylation) and ATP generationsurrogate

Thrombin uniquely activates oxidative phosphorylation as the primary ATP source in human platelets via GPIb-dependent signaling, unlike other agonists that rely predominantly on glycolysis.

Cite This Study

Peña et al. (2017) studied this question.

synapsesocial.com/papers/6a90fe6c152a692a9d92de5a https://doi.org/10.1371/journal.pone.0182374

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Implication

Thrombin may preferentially engage mitochondrial ATP production via GPIb signaling; leaves open whether OxPhos targeting alters platelet function in vivo.

Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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