ANATOMICAL AND FUNCTIONAL CHANGES OF THE HUMAN ERYTHROCYTE CYTOSKELETON ARE MEDIATED BY TUBULIN IN RESPONSE TO INCREASED CALCIUM LEVELS

CARO GUSTAVO; BALACH M.; SANTANDER V; RIVELLI JF; A CAMPETELLI; CASALE C. H.; MONESTEROLO NE

Mendoza

Congreso; SAIB 2022; 2023

SAIB

Erythrocytes affected by age and diseases such as hypertension, diabetes, exhibit abnormally high intracellular Ca2+ ion levels and appear to have altered cytoskeletal properties. In previous research, we observed that tubulin can be found in three fractions within erythrocytes, as membrane-bound, as a soluble fraction, or as part of a structure that can be sedimented by centrifugation. This tubulin may be forming part of the cytoskeleton. We have observed that its differential distribution within these fractions can alter several hemorheological properties, such as the deformability of erythrocytes, the present work studied how this distribution is in turn affected by the increase in Ca2+ levels, another key player in the regulation of the stability of the cytoskeleton of erythrocytes.The results showed that when Ca2+ levels increase in the cell, either due to the addition of the ionophore A23187, due to specific inhibition of plasma membrane Ca2+-ATPase (PMCA), or due to arterial hypertension, tubulin moves to the membrane, erythrocyte deformability decreases, and phosphatidylserine exposure increases. Furthermore, the increase in Ca2+ was associated with aninverse correlation in the distribution of tubulin and spectrin, another important protein of the cytoskeleton. Based on these findings, we propose the existence of a mechanism of action through which higher concentrations of Ca2+ in erythrocytes trigger the migration of tubulin to the membrane, a phenomenon that results in rheological and molecular alterations of the membrane itself, as well as of the integrity of the cytoskeleton.