Essex David W
Department of Medicine Division of Hematology, The University of Texas Health Science Center at San Antonio, 78229, USA.
Antioxid Redox Signal. 2004 Aug;6(4):736-46. doi: 10.1089/1523086041361622.
Disulfide bonds formed in newly synthesized proteins in the endoplasmic reticulum of cells are important for protein structure and stability. Recent research, however, emphasizes a role for thiol-disulfide reactions with disulfide bond rearrangement as a dynamic process in cell and protein function, and in platelet function in particular. Protein disulfide isomerase was found on the platelet surface where it appears to play an important role in the platelet responses of aggregation and secretion, as well as activation of the platelet fibrinogen receptor, the alphaIIbbeta3 integrin. Additionally, sulfhydryl groups in alphaIIbbeta3 have been implicated in the activation of this integrin. Physiologic concentrations of reduced glutathione generate sulfhydryls in alphaIIbbeta3 and potentiate sulfhydryl-dependent reactions in alphaIIbbeta3. Sulfhydryl labeling in alphaIIbbeta3 is inhibited by phenylarsine oxide, a reagent that binds to vicinal thiols. As vicinal thiols are in equilibrium with disulfide bonds, they provide redox-sensitive sites in alphaIIbbeta3 able to respond to external or cytoplasmic reducing equivalents. Furthermore, protein disulfide isomerase and sulfhydryls are now implicated in platelet adhesion by a second platelet integrin, the alpha2beta1 collagen receptor. Most recently, extracellular sulfhydryls in the P2Y12 ADP receptor were found to be required for platelet activation by this receptor. We here provide an overview of this field with a focus on recent developments, and conclude with a working model.
细胞内质网中新合成蛋白质中形成的二硫键对蛋白质结构和稳定性很重要。然而，最近的研究强调了硫醇-二硫键反应以及二硫键重排作为细胞和蛋白质功能，特别是血小板功能中的一个动态过程所起的作用。在血小板表面发现了蛋白质二硫键异构酶，它似乎在血小板聚集和分泌反应以及血小板纤维蛋白原受体αIIbβ3整合素的激活中发挥重要作用。此外，αIIbβ3中的巯基与该整合素的激活有关。生理浓度的还原型谷胱甘肽在αIIbβ3中产生巯基，并增强αIIbβ3中依赖巯基的反应。αIIbβ3中的巯基标记被氧化苯砷抑制，氧化苯砷是一种与邻位硫醇结合的试剂。由于邻位硫醇与二硫键处于平衡状态，它们在αIIbβ3中提供了对氧化还原敏感的位点，能够对外部或细胞质的还原当量做出反应。此外，蛋白质二硫键异构酶和巯基现在被认为与血小板通过另一种血小板整合素α2β1胶原受体的黏附有关。最近发现，P2Y12 ADP受体中的细胞外巯基是该受体激活血小板所必需的。我们在此概述该领域，重点关注最近的进展，并以一个工作模型作为总结。
