Red Blood Cells membrane proteins in patients with Diabetes Mellitus

Abstract

Red blood cells (RBC) are the major cell component of blood. Their main function is to transport oxygen and carbon dioxide, however, besides the main function of RBCs have also the ability to transport immune complexes, express numerous adhesion molecules, and influence leukocytes and platelets margination and adhesion. The molecular architecture of cell membranes plays a key role in the determination of their function. Modifications of RBC membrane components could alter RBC functions and rheological properties.  In this review changes in the protein composition and structure of RBCs membranes in diabetes and their possible diagnostic and prognostic significance are considered.

RBCs membrane proteins are categorized in terms of protein function into three groups: cytoskeletal proteins (spectrin, actin, protein 4.1, etc.), integral structural proteins (band 3, glycophorins (GP), etc.), and anchoring proteins (ankyrin, protein 4.2, etc.). The three principal “cytoskeleton proteins” are spectrin (α and β), actin, and protein 4.1, forming the “junctional complex”, that provides support to the lipid bilayer, and maintains the integrity, shape, and architecture of the red blood cell.  The unusual properties of RBC cytoskeletal proteins form specialized ensembles, provide a unique combination of flexibility and stability RBCs membrane controlling their biogenesis, survival, and function. The extracellular domain of heavily glycosylated sialoglycoproteins (glycophorins, bend 3 protein) at physiological pH are conferring a negative surface charge to RBCs membrane, which plays a crucial role in modulating RBC–RBC interactions, their interactions with vascular endothelium and the other circulating blood cells.

Tightly association of several RBCs' membrane proteins disorders with different pathological processes was identified. In diabetes, RBC membranes are affected by chronic exposure to glucose, triggering their biochemical modifications (glycosylation, oxidation), with subsequent structural and functional disruption of the cell (disorders of their deformability, adhesion to the endothelium), which is further involved in the pathogenesis of diabetes and its complications. The alterations of RBCs membrane proteins might be useful sensitive biomarkers for long-term glycemic control, early diagnosis, or monitoring of disease progression.