AI Article Synopsis
- Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) work together to regulate platelet function and the production of reactive oxygen species (ROS), which are linked to the risk of cardiometabolic diseases.
- The study utilized immunofluorescence microscopy to investigate how PDI and Nox-1 interact and employed various assays to measure platelet activity, confirming their cooperation during activation via the GPVI receptor.
- Results indicated that impairing PDI and Nox-1 simultaneously significantly reduced platelet aggregation and activation, while levels of both proteins were found to increase in individuals with obesity and hypertension, highlighting their role in cardiometabolic risk.
Article Abstract
Background: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors.
Objectives: To establish whether PDI and Nox-1 cooperate to control platelet function.
Methods: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study ( = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors.
Results: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1 platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals.
Conclusions: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004975 | PMC |
| http://dx.doi.org/10.3390/antiox10030497 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Thiol Isomerases Orchestrate Thrombosis and Hemostasis.
Antioxid Redox Signal
November 2021
Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom.
Since protein disulfide isomerase (PDI) was first described in 1963, researchers have shown conclusively that PDI and sibling proteins are quintessential for thrombus formation. PDI, endoplasmic reticulum protein (ERp)5, ERp57, and ERp72 are released from platelets and vascular cells and interact with integrin αIIbβ3 on the outer surface of platelets. At the cell surface they influence protein folding and function, propagating thrombosis and maintaining hemostasis.
View Article and Find Full Text PDFProtein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors.
Antioxidants (Basel)
March 2021
Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading RG6 6AH, UK.
Background: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors.
Objectives: To establish whether PDI and Nox-1 cooperate to control platelet function.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!