التفاصيل البيبلوغرافية
| العنوان: |
Integrating Phenotypic and Chemoproteomic Approaches to Identify Covalent Targets of Dietary Electrophiles in Platelets |
| المؤلفون: |
Ivy A. Guan, Joanna S. T. Liu, Renata C. Sawyer, Xiang Li, Wanting Jiao, Yannasittha Jiramongkol, Mark D. White, Lejla Hagimola, Freda H. Passam, Denise P. Tran, Xiaoming Liu, Simone M. Schoenwaelder, Shaun P. Jackson, Richard J. Payne, Xuyu Liu |
| سنة النشر: |
2024 |
| المجموعة: |
Smithsonian Institution: Figshare |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Pharmacology, Hematology, Biological Sciences not elsewhere classified, unique antiplatelet selectivity, sulfhydryl side chain, related peptide activation, rapid kinetic responder, function remains unclear, electrolytic injury model, arterial flow conditions, identify covalent targets, 23 electrophilic phytochemicals, dietary phytochemicals, covalent modifications, thrombolytic activity, therapeutic mechanisms, substrate specificity, study explores, stroke recanalization, stroke outcomes, significant limitations, results serve, preclinical studies, platelet activity, nuanced modulation, large variety, irreversible engagement, integrating phenotypic |
| الوصف: |
A large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many of these compounds feature electrophilic functionalities that potentially undergo covalent addition to the sulfhydryl side chain of cysteine residues within proteins. However, the impact of such covalent modifications on the platelet activity and function remains unclear. This study explores the irreversible engagement of 23 electrophilic phytochemicals with platelets, unveiling the unique antiplatelet selectivity of sulforaphane (SFN). SFN impairs platelet responses to adenosine diphosphate (ADP) and a thromboxane A2 receptor agonist while not affecting thrombin and collagen-related peptide activation. It also substantially reduces platelet thrombus formation under arterial flow conditions. Using an alkyne-integrated probe, protein disulfide isomerase A6 (PDIA6) was identified as a rapid kinetic responder to SFN. Mechanistic profiling studies revealed SFN’s nuanced modulation of PDIA6 activity and substrate specificity. In an electrolytic injury model of thrombosis, SFN enhanced the thrombolytic activity of recombinant tissue plasminogen activator (rtPA) without increasing blood loss. Our results serve as a catalyst for further investigations into the preventive and therapeutic mechanisms of dietary antiplatelets, aiming to enhance the clot-busting power of rtPA, currently the only approved therapeutic for stroke recanalization that has significant limitations. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Integrating_Phenotypic_and_Chemoproteomic_Approaches_to_Identify_Covalent_Targets_of_Dietary_Electrophiles_in_Platelets/25102742 |
| DOI: |
10.1021/acscentsci.3c00822.s004 |
| الاتاحة: |
https://doi.org/10.1021/acscentsci.3c00822.s004 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.B43517FC |
| قاعدة البيانات: |
BASE |