Accessibility navigation

The protein disulphide isomerase inhibitor CxxCpep modulates oxidative burst and mitochondrial function in platelets

Gaspar, R. S., Mansilla, S., Vieira, V. A., da Silva, L. B., Gibbins, J. M. ORCID:, Castro, L., Trostchansky, A. and de A. Paes, A. M. (2021) The protein disulphide isomerase inhibitor CxxCpep modulates oxidative burst and mitochondrial function in platelets. Free Radical Biology and Medicine, 172. pp. 668-674. ISSN 0891-5849

Text - Accepted Version
· Available under License Creative Commons Attribution Non-commercial No Derivatives.
· Please see our End User Agreement before downloading.


It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1016/j.freeradbiomed.2021.07.011


Background: We have previously described CxxCpep, a peptide with anti-platelet properties that inhibits peri/epicellular protein disulphide isomerase (pecPDI) by forming a mixed disulfide bond with Cys400 within the pecPDI active site. Objectives: Here we sought to determine if pecPDI targeted by CxxCpep is relevant to redox mechanisms downstream of the collagen receptor GPVI in platelets. Methods and Results: Restriction of effects of CxxCpep to the platelet surface was confirmed by LC-MS/MS following cell fractionation. Platelet aggregation was measured in platelet-rich plasma (PRP) incubated with 30 μM CxxCpep or vehicle. CxxCpep inhibited collagen-induced platelet aggregation but exerted no effect in TRAP-6-stimulated platelets. PRP was incubated with DCFDA to measure oxidative burst upon platelet adhesion to collagen. Results showed that CxxCpep decreased oxidative burst in platelets adhered to immobilized collagen while the number of adherent cells was unaffected. Furthermore, flow cytometry studies using a FITC-maleimide showed that the GPVI agonist CRP stimulated an increase in free thiols on the platelet outer membrane, which was inhibited by CxxCpep. Finally, CxxCpep inhibited platelet mitochondrial respiration upon activation with collagen, but not with thrombin. Conclusions: Our data suggest that pecPDI is a potential modulator of GPVI-mediated redox regulation mechanisms and that CxxCpep can be further exploited as a template for new antiplatelet compounds.

Item Type:Article
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:99182
Uncontrolled Keywords:Platelets; Protein Disulphide Isomerase; Collagen; Platelet Inhibitor; Redox biology


Downloads per month over past year

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation