Zinc regulates reactive oxygen species generation in platelets

Lopes-Pires, Maria E. and Ahmed, Niaz S. and Vara, Dina and Gibbins, Jonathan M. and Pula, Giordano and Pugh, Nicholas (2021) Zinc regulates reactive oxygen species generation in platelets. Platelets, 32 (3). pp. 368-377. ISSN 1369-1635

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Official URL: https://doi.org/10.1080/09537104.2020.1742311


Vascular complications resulting from atherosclerosis development are a major cause of death. Reactive oxygen species (ROS) are produced by platelets during activation, and have been demonstrated to positively regulate platelet activatory responses. Zn2+ is also an important haemostatic cofactor in platelets, acting both as a platelet agonist and secondary messenger. Whilst the effect of Zn2+-dependent signalling mechanisms on ROS production in nucleated cells has been demonstrated, comparable roles in platelets have yet to be investigated. In this study we investigate the relationship between fluctuations in cytosolic Zn2 [Zn2+]i and platelet ROS production. Agonist-evoked ROS production, GSH levels and GPx activity are abrogated in platelets treated with the Zn2+-chelator, TPEN. Conversely, increasing platelet [Zn2+]i using Zn2+ ionophores potentiated ROS generation and decreased GSH levels and GPx activity. Zn2+-dependent ROS production was sensitive to pretreatment with DPI or mitoTEMPO, a NADPH oxidase and mitochondria inhibitors respectively. Increasing [Zn2+]i resulted in increases of Erk1/2 and JNK phosphorylation. Our data are consistent with a functional association between [Zn2+]i and ROS production in platelets that could influence thrombus formation in a clinical context.

Item Type: Journal Article
Keywords: Zinc, platelets, ROS, signal transduction, thrombosis
Faculty: Faculty of Science & Engineering
Depositing User: Lisa Blanshard
Date Deposited: 30 Mar 2020 14:28
Last Modified: 19 Apr 2021 15:42
URI: https://arro.anglia.ac.uk/id/eprint/705368

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