The role of protein sulfhydryl groups and protein disulfides of the platelet surface in aggregation processes involving thiol exchange reactions |
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| Authors: | Antonios Margaritis Raffaella Priora Simona Frosali Danila Di Giuseppe Domenico Summa Lucia Coppo Anna Di Stefano Paolo Di Simplicio |
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| Institution: | 1. Department of Neuroscience, Pharmacology Unit, University of Siena, Via Aldo Moro 4, 53100 Siena, Italy;2. Department of Molecular Biology, University of Siena, 53100 Siena, Italy;1. Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation;2. Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka, Russian Federation;1. Physiology Research Group, Federal University of Pampa, Uruguaiana, RS, Brazil;2. Cardiovascular Physiology Research Group, Federal University of Pampa, Uruguaiana, RS, Brazil;3. Federal University of Espirito Santo, Vitória, ES, Brazil;4. Brain Institute, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil;1. Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, United States;2. USF Health Byrd Alzheimer’s Institute, Tampa, FL 33613, United States;3. Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, United States;3. From the Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 and;4. the Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702;1. Department of Food Science, Faculty of Science, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg C, Denmark;2. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen N, 2200 Denmark |
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| Abstract: | Blood platelets are central to haemostasis and platelet aggregation is considered to be a direct index of platelet function. Although protein disulfides (PSSP) are structural components of most proteins, current evidence suggests that PSSP work together with protein SH groups (PSH) to activate various platelet functions in dynamic processes involving thiol/disulfide exchange reactions.Based on these assumptions, we performed experiments to demonstrate how PSH and PSSP are involved in platelet aggregation and how modifications of PSH and PSSP concentrations on the platelet surface by N-ethylmaleimide (NEM) (a PSH-blocking reagent) and dithiothreitol (DTT) (a PSSP-reducing reagent), respectively, may condition platelet susceptibility in protein rich plasma and washed platelets and integrin αIIbβ3 conformation. Our data strongly suggest that the PSH blockage and the PSSP reduction of the platelet surface are deeply involved in aggregation processes evoked in protein rich plasma and washed platelets by ADP and collagen; that endogenous thiols (e.g. GSH) may interfere with NEM actions; that NEM and DTT, acting on preexisting PSH and PSSP of active platelets have opposite conformational changes on integrin αIIbβ3 conformation. Although the precise mechanism and the populations of specific PSH and PSSP involved remain unresolved, our data support the notion that PSH and PSSP of the platelet surface are involved in platelet activation by thiol exchange reactions. A plausible molecular mechanism of PSH and PSSP recruitment during thiol exchange reactions is here proposed. |
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