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dc.contributor.authorWalsh, T.
dc.contributor.authorBerndt, Michael
dc.contributor.authorCarrim, N.
dc.contributor.authorCowman, J.
dc.contributor.authorKenny, D.
dc.contributor.authorMetharom, Pat
dc.identifier.citationWalsh, T. and Berndt, M. and Carrim, N. and Cowman, J. and Kenny, D. and Metharom, P. 2014. The role of Nox1 and Nox2 in GPVI-dependent platelet activation and thrombus formation. Redox Biology. 2: pp. 178-186.

Background: Activation of the platelet-specific collagen receptor, glycoprotein (GP) VI, induces intracellular reactive oxygen species (ROS) production; however the relevance of ROS to GPVI-mediated platelet responses remains unclear. Objective: The objective of this study was to explore the role of the ROS-producing NADPH oxidase (Nox)1 and 2 complexes in GPVI-dependent platelet activation and collagen-induced thrombus formation. Methods and results: ROS production was measured by quantitating changes in the oxidation-sensitive dye, H2DCF-DA, following platelet activation with the GPVI-specific agonist, collagen related peptide (CRP). Using a pharmacological inhibitor specific for Nox1, 2-acetylphenothiazine (ML171), and Nox2 deficient mice, we show that Nox1 is the key Nox homolog regulating GPVI-dependent ROS production. Nox1, but not Nox2, was essential for CRP-dependent thromboxane (Tx)A2 production, which was mediated in part through p38 MAPK signaling; while neither Nox1 nor Nox2 was significantly involved in regulating CRP-induced platelet aggregation/integrin αIIbβ3 activation, platelet spreading, or dense granule and α-granule release (ATP release and P-selectin surface expression, respectively). Ex-vivo perfusion analysis of mouse whole blood revealed that both Nox1 and Nox2 were involved in collagen-mediated thrombus formation at arterial shear. Conclusion: Together these results demonstrate a novel role for Nox1 in regulating GPVI-induced ROS production, which is essential for optimal p38 activation and subsequent TxA2 production, providing an explanation for reduced thrombus formation following Nox1 inhibition.

dc.publisherElsevier BV
dc.titleThe role of Nox1 and Nox2 in GPVI-dependent platelet activation and thrombus formation
dc.typeJournal Article
dcterms.source.titleRedox Biology
curtin.accessStatusOpen access via publisher
curtin.facultyFaculty of Health Sciences

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