Targeting spectrin redox switches to regulate the mechanoproperties of red blood cells
Author:
Barbarino Frederik1, Wäschenbach Lucas2ORCID, Cavalho-Lemos Virginia1, Dillenberger Melissa3, Becker Katja3, Gohlke Holger24ORCID, Cortese-Krott Miriam M.1ORCID
Affiliation:
1. Myocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Vascular Medicine , Medical Faculty, Heinrich Heine University , Postfach 128, Universitätsstrasse 1 , D-40225 , Düsseldorf , Germany 2. Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University , Universitätsstrasse 1 , D-40225 , Düsseldorf , Germany 3. Biochemistry and Molecular Biology , Interdisciplinary Research Center, Justus Liebig University , D-35392 , Giessen , Germany 4. John von Neumann Institute for Computing (NIC), Jülich Supercomputing Centre (JSC), Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich GmbH , D-52425 , Jülich , Germany
Abstract
Abstract
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.
Funder
Deutsche Forschungsgemeinschaft
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
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