دورية أكاديمية
The protein disulphide isomerase inhibitor CxxCpep modulates oxidative burst and mitochondrial function in platelets.
| العنوان: | The protein disulphide isomerase inhibitor CxxCpep modulates oxidative burst and mitochondrial function in platelets. |
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| المؤلفون: | Gaspar RS; Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UK; Laboratory of Experimental Physiology, Department of Physiology, Biological and Health Sciences Centre, Federal University of Maranhão, São Luís, Brazil; Laboratory of Vascular Biology, Health Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil., Mansilla S; Departamento de Métodos Cuantitativos y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Departamento de Bioquímica y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay., Vieira VA; Laboratory of Experimental Physiology, Department of Physiology, Biological and Health Sciences Centre, Federal University of Maranhão, São Luís, Brazil., da Silva LB; Laboratory of Experimental Physiology, Department of Physiology, Biological and Health Sciences Centre, Federal University of Maranhão, São Luís, Brazil; Health Sciences Graduate Program, Biological and Health Sciences Centre, Federal University of Maranhão, São Luís, Brazil., Gibbins JM; Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UK., Castro L; Departamento de Bioquímica y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay., Trostchansky A; Departamento de Bioquímica y Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay., Paes AMA; Laboratory of Experimental Physiology, Department of Physiology, Biological and Health Sciences Centre, Federal University of Maranhão, São Luís, Brazil; Health Sciences Graduate Program, Biological and Health Sciences Centre, Federal University of Maranhão, São Luís, Brazil. Electronic address: marcuspaes@ufma.br. |
| المصدر: | Free radical biology & medicine [Free Radic Biol Med] 2021 Aug 20; Vol. 172, pp. 668-674. Date of Electronic Publication: 2021 Jul 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Tarrytown, NY : Elsevier Science Original Publication: New York : Pergamon, c1987- |
| مواضيع طبية MeSH: | Blood Platelets*/metabolism , Protein Disulfide-Isomerases*/metabolism, Chromatography, Liquid ; Mitochondria/metabolism ; Platelet Activation ; Platelet Aggregation ; Platelet Membrane Glycoproteins/metabolism ; Respiratory Burst ; Tandem Mass Spectrometry |
| مستخلص: | 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. (Copyright © 2021 Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | MR/J002666/1 United Kingdom MRC_ Medical Research Council; RG/15/2/31224 United Kingdom BHF_ British Heart Foundation |
| فهرسة مساهمة: | Keywords: Collagen; Platelet inhibitor; Platelets; Protein disulphide isomerase; Redox biology |
| المشرفين على المادة: | 0 (Platelet Membrane Glycoproteins) EC 5.3.4.1 (Protein Disulfide-Isomerases) |
| تواريخ الأحداث: | Date Created: 20210712 Date Completed: 20210826 Latest Revision: 20210924 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.freeradbiomed.2021.07.011 |
| PMID: | 34252541 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-4596 |
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| DOI: | 10.1016/j.freeradbiomed.2021.07.011 |