INVESTIGAÇÃO DA ATIVIDADE ANTIAGREGANTE IN VITRO DE PEPTÍDEOS INIBIDORES DA PROTEÍNA DISSULFETO ISOMERASE

• Autor(a) principal: SENA, Elyjany Morais Lima
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFMA
• Texto Completo: http://tedebc.ufma.br:8080/jspui/handle/tede/578
• topic: difosfato de adenosina; agregação plaquetária; compostos de sulfidrila; plaquetas; adenosine diphosphate; platelet aggregation; sulfhydryl compounds; platelets; CIENCIAS BIOLOGICAS

Protein disulfide isomerase (PDI) plays an important role in platelet aggregation involving thiol containing surface proteins in both dependent pathways and independent of ADP. Recently it has been shown that one dodecapeptide (CXXC) containing the catalytic motif PDI was able to decrease the reductase activity of PDI opening the perspective of using the same as antithrombotic therapeutic agent. This study aimed to investigate the effects of peptides PDI - like on platelet aggregation in vitro and molecular mechanism of action of the same. For in silico analysis using a molecular docking program, it was observed that the CXXC peptide as well as its control peptide, scrambled (SCR) and AXXA were all capable of binding to the substrate site of the lligação PDI. Posteriorly, Western blot, it was demonstrated that the peptide CXXC (25  M) induced a slight but significant reduction of free thiols marking PDI suggesting physical association between the peptide and the protein. The same was not observed in samples incubated with Scr and AXXA peptides at the same concentration. In platelet aggregation assays, the platelet-rich plasma (PRP) was pre-incubated with the CXXC, Scr and AXXA peptides using ADP (5  M) as aggregating agent. CXXC found that the peptide reduced the maximum aggregation by 14%, 27% and 30% at concentrations of 3, 10 and 30μM, respectively. The Scr AXXA peptide and the peptide had no effect on platelet aggregation induced by ADP in the same concentrations. Thus, all the data presented here suggest that the CXXC peptide is associated with PDI surface and partially inhibits platelet aggregation via mechanisms mediated by thiol-disulfide exchange.