ArticleBritish journal of pharmacology2013
The novel NOX inhibitor 2-acetylphenothiazine impairs collagen-dependent thrombus formation in a GPVI-dependent manner.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- Oxidative Stress Induced by Cortisol in Human Platelets.International journal of molecular sciences · 2024Article
- Inside the Mechanism of Action of Three Pyrazole Derivatives in Human Platelets and Endothelial Cells.Antioxidants (Basel, Switzerland) · 2023Article
- Shear and Integrin Outside-In Signaling Activate NADPH-Oxidase 2 to Promote Platelet Activation.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Diabetes and Thrombosis: A Central Role for Vascular Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Article
- Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors.Antioxidants (Basel, Switzerland) · 2021Article
- NADPH Oxidases Are Required for Full Platelet Activation In Vitro and Thrombosis In Vivo but Dispensable for Plasma Coagulation and Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Oxidative Stress and Preeclampsia-Associated Prothrombotic State.Antioxidants (Basel, Switzerland) · 2020Review
- Synthesis of Novel Chalcone-Based Phenothiazine Derivatives as Antioxidant and Anticancer Agents.Molecules (Basel, Switzerland) · 2020Article
- p47phox deficiency impairs platelet function and protects mice against arterial and venous thrombosis.Redox biology · 2020Article
- Lectin-induced oxidative stress in human platelets.Redox biology · 2020Article
- VAS2870 and VAS3947 attenuate platelet activation and thrombus formation via a NOX-independent pathway downstream of PKC.Scientific reports · 2019Article
- Nox1 downregulators: A new class of therapeutics.Steroids · 2019Review
- Article
- Acute bilirubin ditaurate exposure attenuates ex vivo platelet reactive oxygen species production, granule exocytosis and activation.Redox biology · 2019Article
- Amyloid PeptideOxidative medicine and cellular longevity · 2019Article
- The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders.International journal of molecular sciences · 2018Review
- Small molecule targeting the Rac1-NOX2 interaction prevents collagen-related peptide and thrombin-induced reactive oxygen species generation and platelet activation.Journal of thrombosis and haemostasis : JTH · 2018Article
- Regulation of platelet activation and thrombus formation by reactive oxygen species.Redox biology · 2018Review
- Direct Activation of NADPH Oxidase 2 by 2-Deoxyribose-1-Phosphate Triggers Nuclear Factor Kappa B-Dependent Angiogenesis.Antioxidants & redox signaling · 2018Article
- MEF2D Mediates the Neuroprotective Effect of Methylene Blue Against Glutamate-Induced Oxidative Damage in HT22 Hippocampal Cells.Molecular neurobiology · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeNADPH oxidases (NOXs) contribute to platelet activation by a largely unknown mechanism. Here, we studied the effect of the novel NOX inhibitor 2-acetylphenothiazine (2-APT) on human platelet functional responses and intracellular signaling pathways. EXPERIMENTAL APPROACH: The generation of superoxide ions was assessed by single cell imaging on adhering platelets using dihydroethidium (DHE), while other reactive oxygen species (ROS) were detected with 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate (CM-H(2)-DCFDA). Whole blood thrombus formation, washed platelet aggregation, integrin αIIbβ3 inside-out signalling, Syk phosphorylation and PKC activation were analysed to understand the functional consequences of NOX inhibition by 2-APT in platelets. KEY
resultsSuperoxide ion generation stimulated by platelet adhesion on collagen and fibrinogen was significantly inhibited by 2-APT in concentration-dependent manner (IC(50) = 306 nM and 227 nM, respectively), whereas cumulative ROS accumulation was not affected by this pharmacological agent. 2-APT also abolished collagen-dependent whole blood thrombus formation and washed platelet aggregation in response to collagen but not thrombin. The activation of integrin αIIbβ3 and PKC in response to the GPVI-specific agonist collagen-related peptide (CRP) was significantly reduced, whereas the same responses to thrombin were not significantly affected by 2-APT. Finally, Syk activation in response to collagen but not thrombin was inhibited by 2-APT. CONCLUSIONS AND IMPLICATIONS: Taken together, our results suggest that 2-APT attenuates GPVI-specific signalling and is a novel inhibitor of collagen-induced platelet responses. Therefore, NOXs could represent a novel target for the discovery of anti-thrombotic drugs.
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