Abstract 19967: Differential Roles of the NADPH-Oxidase 1 and 2 in Platelet Activation and Thrombosis
| Autor: | Jaehyung Cho, Bo Shen, Aleksandra Stojanovic-Terpo, Michael K Delaney, Xiaoping Du, Kyungho Kim, Brian Estevez, Masuko Ushio-Fukai |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
chemistry.chemical_classification
Gene isoform Reactive oxygen species Nicotinamide business.industry NADPH Oxidase 1 medicine.disease Thrombosis chemistry.chemical_compound Biochemistry chemistry Physiology (medical) cardiovascular system medicine Platelet Platelet activation Cardiology and Cardiovascular Medicine business circulatory and respiratory physiology |
| Zdroj: | Circulation. 132 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.132.suppl_3.19967 |
| Popis: | Objective: Reactive oxygen species (ROS) generated from activated platelets is known to regulate platelet activation. However, it remains unclear whether and how different isoforms of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases (NOXs) play roles in different platelet activation pathways. Here we investigated the role of NOX1 and NOX2 in different platelet activation pathways using NOX1 and NOX2 knockout mice. Approach and Results: NOX1-/- platelets showed selective defects in G protein coupled receptor (GPCR)-mediated platelet activation induced by thrombin, protease-activated receptor 4 agonist peptide (PAR4AP) and thromboxane A2 analog U46619, but was not affected in platelet activation induced by collagen-related peptide (CRP), a glycoprotein VI (GPVI) agonist. In contrast, NOX2-/- platelets showed potent inhibition of CRP-induced platelet activation, and also showed partial inhibition of thrombin-induced platelet aggregation and secretion. Consistently, production of reactive oxygen species (ROS) was inhibited in NOX1-/- platelets stimulated with thrombin, but not CRP, whereas NOX2-/- platelets showed reduced ROS generation induced by CRP or thrombin. Interestingly, laser-induced arterial thrombosis was impaired in NOX2-/- mice, and in thrombocytopenic mice transfused with NOX2-/- platelets, suggesting an important role for NOX2-dependent platelet ROS production in the laser-induced injury model of thrombosis. Conclusions: NOX1 and NOX2 play differential roles in different platelet activation pathways: NOX1 mediates GPCR-mediated ROS production and platelet activation, whereas NOX2 plays a general role in GPVI- and GPCR-induced ROS production and platelet activation in vitro , and in laser-induced thrombosis in vivo . |
| Databáze: | OpenAIRE |
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