Tubulin as a regulator of Phosphatidylserine exposure in red blood cells and its impact on haemorrheology.

BALACH, MELISA M.; ETCHEVERRY, MICAELA; MONESTEROLO NOELIA E; SANTANDER, VERÓNICA S.; RIVELLI, JUAN F.; URETA MIRALLA, LUCÍA B.; CASALE, CESAR H.; CAMPETELLI, ALEXIS N.

Mendoza

Congreso; Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2022

SAIB

Previously, our group showed that in erythrocytes from diabetic and hypertensive patients, plasma membrane tubulin is increased when compared with erythrocytes from normal subjects. At the plasma membrane, tubulin inhibits several P-ATPases, including lipid flippases, producing an increase in phosphatidylserine (PS) exposure. Since in normal erythrocytes, the progressive PS exposure becomes a senescence signal that leads to macrophage-mediated phagocytosis during eryptosis, we set out to determine whether the increase in membrane tubulin influences erythrocytes lifespan and whether this effect contributes to the development of anemia. For this, we performed an experiment with rats where the content of membrane tubulin in erythrocytes was naturally altered ((Wistar Kyoto strain (WK, normotensive), diabeticized WK (streptozotocin treatment) and SHR (spontaneously hypertensive rats)), or modified pharmacologically by Taxol or Tyrosine treatment. During a period of 7 weeks we monitored the erythrocyte half-life time, erythrocyte PS exposure and the reticulocyte count in peripheral blood, among other parameters. We found that in erythrocytes from SHR, diabetic as well as in WK animals treated with Taxol, the PS exposure was greater than in WK and SHR rats treated with Tyrosine. Accordingly, the erythrocyte half-life was shorter in SHR, diabetics and Taxol-treated WK than erythrocytes from WK rats, showing an inverse correlation between PS exposure and erythrocyte half-life time. Furthermore, those animal groups with increased PS exposure and shortened erythrocyte half-life time displayed increased reticulocyte count. Finally, the blood count only displayed a mild decrease in RBC count, hematocrit and haemoglobin values, for WK treated with taxol, suggesting a mild anemia. These results suggest that, in red blood cells, plasma membrane tubulin can regulate the lifespan of these cells through a mechanism that involves the regulation of lipid flippases.