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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Gaspar, Renato S. [1, 2, 3] ; Mansilla, Santiago [4, 5] ; Vieira, Victor A. [2, 6] ; Silva, Ludmila B. da [2, 7] ; Gibbins, Jonathan M. [1] ; Castro, Laura [4, 6] ; Trostchansky, Andres [4, 6] ; Paes, Antonio Marcus de A. [2, 7]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Reading, Sch Biol Sci, Inst Cardiovasc & Metab Res, Reading, Berks - England
[2] Univ Fed Maranhao, Biol & Hlth Sci Ctr, Dept Physiol, Lab Expt Physiol, Sao Luis, Maranhao - Brazil
[3] Univ Sao Paulo, Sch Med, Hlth Inst InCor, Lab Vasc Biol, Sao Paulo - Brazil
[4] Univ Republica, Fac Med, Dept Bioquim, Montevideo - Uruguay
[5] Univ Republica, Fac Med, Dept Metodos Cuantitat, Montevideo - Uruguay
[6] Univ Republica, Fac Med, Ctr Invest Biomed CEINBIO, Montevideo - Uruguay
[7] Univ Fed Maranhao, Hlth Sci Grad Program, Biol & Hlth Sci Ctr, Sao Luis, Maranhao - Brazil
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: Free Radical Biology and Medicine; v. 172, p. 668-674, AUG 20 2021.
Citações Web of Science: 0
Resumo

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 mu M 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. (AU)

Processo FAPESP: 20/15944-8 - Investigação da proteína disulfeto isomerase peri/epicelular como um novo regulador da interação plaqueta-endotélio em normoglicemia e Diabetes
Beneficiário:Renato Simões Gaspar
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado