ArticlePloS one
RhoA and Rac1 GTPases Differentially Regulate Agonist-Receptor Mediated Reactive Oxygen Species Generation in Platelets.
Article in PloS one. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Design of a modified platelet immunofluorescence test to assess platelet-reactive antibody burden and its association with platelet functional exhaustion and clinical features in chronic immune thrombocytopenia.British journal of haematology · 2026Article
- RAP1-RHO small GTPase cross-talk mediates integrindependent and -independent platelet procoagulant response.Haematologica · 2026Article
- A design for an efficient functional panel that determines platelet exhaustion levels to differentiate responder and non-responder ITP patients.Scientific reports · 2025Article
- Redox Control in Platelet Activity and Therapy.Antioxidants (Basel, Switzerland) · 2025Review
- Platelets and diseases: signal transduction and advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- The effect of modulating platelet reactive oxygen species by the addition of antioxidants to prevent clearance of cold-stored platelets.Hematology, transfusion and cell therapy · 2024Article
- Exploring bias in platelet P2YBritish journal of pharmacology · 2024Review
- Stimulation of platelet P2YBritish journal of pharmacology · 2024Article
- Integrin βNature communications · 2023Article
- NFIXing Cancer: The Role of NFIX in Oxidative Stress Response and Cell Fate.International journal of molecular sciences · 2023Review
- Structure-Activity Relationship Analysis of Rhosin, a RhoA GTPase Inhibitor, Reveals a New Class of Antiplatelet Agents.International journal of molecular sciences · 2023Article
- Rho GTPase Signaling in Platelet Regulation and Implication for Antiplatelet Therapies.International journal of molecular sciences · 2023Review
- Review
- Pharmacologic targeting of Cdc42 GTPase by a small molecule Cdc42 activity-specific inhibitor prevents platelet activation and thrombosis.Scientific reports · 2021Article
- Shear and Integrin Outside-In Signaling Activate NADPH-Oxidase 2 to Promote Platelet Activation.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Small G-protein RhoA is a potential inhibitor of cardiac fast sodium current.Journal of physiology and biochemistry · 2021Article
- Antioxidant prevents clearance of hemostatically competent platelets after long-term cold storage.Transfusion · 2021Article
- The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function.Nature communications · 2020Article
- Pathways Governing Polyethylenimine Polyplex Transfection in Microporous Annealed Particle Scaffolds.Bioconjugate chemistry · 2019Article
- Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Agonist induced generation of reactive oxygen species (ROS) by NADPH oxidases (NOX) enhances platelet aggregation and hence the risk of thrombosis. RhoA and Rac1 GTPases are involved in ROS generation by NOX in a variety of cells, but their roles in platelet ROS production remain unclear. In this study we used platelets from RhoA and Rac1 conditional knockout mice as well as human platelets treated with Rhosin and NSC23767, rationally designed small molecule inhibitors of RhoA and Rac GTPases, respectively, to better define the contributions of RhoA and Rac1 signaling to ROS generation and platelet activation. Treatment of platelets with Rhosin inhibited: (a) U46619 induced activation of RhoA; (b) phosphorylation of p47phox, a critical component of NOX; (c) U46619 or thrombin induced ROS generation; (d) phosphorylation of myosin light chain (MLC); (e) platelet shape change; (f) platelet spreading on immobilized fibrinogen; and (g) release of P-selectin, secretion of ATP and aggregation. Conditional deletion of RhoA or Rac1 gene inhibited thrombin induced ROS generation in platelets. Addition of Y27632, a RhoA inhibitor, NSC23766 or Phox-I, an inhibitor of Rac1-p67phox interaction, to human platelets blocked thrombin induced ROS generation. These data suggest that: (a) RhoA/ROCK/p47phox signaling axis promotes ROS production that, at least in part, contributes to platelet activation in conjunction with or independent of the RhoA/ROCK mediated phosphorylation of MLC; and (b) RhoA and Rac1 differentially regulate ROS generation by inhibiting phosphorylation of p47phox and Rac1-p67phox interaction, respectively.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.