ArticleAntioxidants & redox signaling2014
Reactive oxygen species play a critical role in collagen-induced platelet activation via SHP-2 oxidation.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Jak2 V617F clonal hematopoiesis promotes arterial thrombosis via platelet activation and cross talk.Blood · 2024Pooled it
- Enzymatic and non-enzymatic oxidation of fibrillar collagen.Redox report : communications in free radical research · 2026Review
- Platelet mitochondria dysfunction in diabetes mellitus: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- A defined isothiocyanate mixture suppresses platelet signaling and metabolism to limit thrombosisFrontiers in immunology · 2026Article
- NADPH oxidase 2 inhibitor GSK2795039 exerts antiplatelet and antithrombotic activity.Scientific reports · 2025Article
- Living on the Edge: ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target.Antioxidants (Basel, Switzerland) · 2025Review
- Increased Circulating Extracellular Superoxide Dismutase Attenuates Platelet-Neutrophil Interactions.American journal of respiratory cell and molecular biology · 2025Article
- Signalling Network Analysis of Blood Mononuclear Cells From Clinical Samples by Bivariate Correlation.Journal of cellular and molecular medicine · 2025Article
- Aging-associated changes in immunological parameters: Implications for COVID-19 immune response in the elderly.Physiological reports · 2025Review
- Review
- Oroxylin A reverses SHP-2 oxidative inactivation in GPVI signaling to suppress platelet activation and thrombus formation.Thrombosis journal · 2025Article
- Acrylamide and bisphenol A: two plastic additives increase platelet activation, via oxidative stress.Frontiers in pharmacology · 2025Article
- Efficacy of neutral electrolyzed water vs. common topical antiseptics in the healing of full‑thickness burn: Preclinical trial in a mouse model.Biomedical reports · 2024Article
- Understanding the Role of Oxidative Stress in Platelet Alterations and Thrombosis Risk among Frail Older Adults.Biomedicines · 2024Review
- Severe fever with thrombocytopenia syndrome virus induces platelet activation and apoptosis via a reactive oxygen species-dependent pathway.Redox biology · 2023Article
- Mast Cells as a Potential Target of Molecular Hydrogen in Regulating the Local Tissue Microenvironment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- An optimized herbal medicine containingJournal of traditional and complementary medicine · 2023Article
- Pyroptosis in platelets: Thrombocytopenia and inflammation.Journal of clinical laboratory analysis · 2023Review
- Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis.Frontiers in pharmacology · 2023Article
- Diindolylmethane Ameliorates Ischemic Stroke-Induced Brain Injury by Peripheral and Central Mechanisms.Current neurovascular research · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe collagen-stimulated generation of reactive oxygen species (ROS) regulates signal transduction in platelets, although the mechanism is unclear. The major targets of ROS include protein tyrosine phosphatases (PTPs). ROS-mediated oxidation of the active cysteine site in PTPs abrogates the PTP catalytic activity. The aim of this study was to elucidate whether collagen-induced ROS generation leads to PTP oxidation, which promotes platelet stimulation.
resultsSH2 domain-containing PTP-2 (SHP-2) is oxidized in platelets by ROS produced upon collagen stimulation. The oxidative inactivation of SHP-2 leads to the enhanced tyrosine phosphorylation of spleen tyrosine kinase (Syk), Vav1, and Bruton's tyrosine kinase (Btk) in the linker for the activation of T cells signaling complex, which promotes the tyrosine phosphorylation-mediated activation of phospholipase Cγ2 (PLCγ2). Moreover, we found that, relative to wild-type platelets, platelets derived from glutathione peroxidase 1 (GPx1)/catalase double-deficient mice showed enhanced cellular ROS levels, oxidative inactivation of SHP-2, and tyrosine phosphorylation of Syk, Vav1, Btk, and PLCγ2 in response to collagen, which subsequently led to increased intracellular calcium levels, degranulation, and integrin αIIbβ3 activation. Consistent with these findings, GPx1/catalase double-deficiency accelerated the thrombotic response in FeCl3-injured carotid arteries. INNOVATION: The present study is the first to demonstrate that SHP-2 is targeted by ROS produced in collagen-stimulated platelets and suggests that a novel mechanism for the regulation of platelet activation by ROS is due to oxidative inactivation of SHP-2.
conclusionWe conclude that collagen-induced ROS production leads to SHP-2 oxidation, which promotes platelet activation by upregulating tyrosine phosphorylation-based signal transduction.
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