Myocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University, Postfach 128, Universitätsstrasse 1, D-40225, Düsseldorf, Germany.
Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Universitätsstrasse 1, D-40225, Düsseldorf, Germany.
Biol Chem. 2020 Dec 2;402(3):317-331. doi: 10.1515/hsz-2020-0293. Print 2021 Feb 23.
The mechanical properties of red blood cells (RBCs) are fundamental for their physiological role as gas transporters. RBC flexibility and elasticity allow them to survive the hemodynamic changes in the different regions of the vascular tree, to dynamically contribute to the flow thereby decreasing vascular resistance, and to deform during the passage through narrower vessels. RBC mechanoproperties are conferred mainly by the structural characteristics of their cytoskeleton, which consists predominantly of a spectrin scaffold connected to the membrane via nodes of actin, ankyrin and adducin. Changes in redox state and treatment with thiol-targeting molecules decrease the deformability of RBCs and affect the structure and stability of the spectrin cytoskeleton, indicating that the spectrin cytoskeleton may contain redox switches. In this perspective review, we revise current knowledge about the structural and functional characterization of spectrin cysteine redox switches and discuss the current lines of research aiming to understand the role of redox regulation on RBC mechanical properties. These studies may provide novel functional targets to modulate RBC function, blood viscosity and flow, and tissue perfusion in disease conditions.
红细胞（RBC）的力学特性是其作为气体转运器的生理功能的基础。RBC 的柔韧性和弹性使它们能够在血管树的不同区域的血液动力学变化中存活下来，通过动态地促进流动从而降低血管阻力，并在通过较窄的血管时变形。RBC 的力学特性主要取决于其细胞骨架的结构特征，该细胞骨架主要由连接到膜上的血影蛋白支架组成，通过肌动蛋白、锚蛋白和钙调蛋白的连接点与膜相连。氧化还原状态的变化和巯基靶向分子的处理会降低 RBC 的变形能力，并影响血影蛋白细胞骨架的结构和稳定性，这表明血影蛋白细胞骨架可能包含氧化还原开关。在这篇观点综述中，我们回顾了当前关于血影蛋白半胱氨酸氧化还原开关的结构和功能特征的知识，并讨论了旨在了解氧化还原调节对 RBC 力学特性的作用的当前研究方向。这些研究可能为调节 RBC 功能、血液粘度和流动以及疾病状态下的组织灌注提供新的功能靶点。
