Prevention by Pentoxifylline of Transient Ca²⁺ Accumulation and Transglutaminase Activation in Rat Erythrocytes

Abstract

The authors have examined the effects of pentoxifylline, a drug used to improve peripheral blood flow in patients with vascular disorders, on shear-induced periodic Ca2+ entry and its consequences in the rat erythrocyte. To study the effects of periodic Ca2+ entry on Ca2+ dependent processes, erythrocytes, with and without pentoxifylline, were subjected to rotational shear produced by swirling-cell suspensions in an isosmotic medium for 5-second intervals. Pulses of increasing duration from 5-30 seconds promoted increased accumulation of 45Ca2+; intermittent 5 sec pulses, at 10-minute intervals, produced a stepwise accumulation of 45Ca2+. Ca2+ accumulation was accompanied by elevated Ca2+ dependent transglutaminase. Shear induced Ca2+ entry and the increase in transglutaminase activity was reduced in cells treated with pentoxifylline. These findings suggest that pentoxifylline can reduce shear induced periodic Ca2+ entry that leads to transient activation of Ca2+ dependent transglutaminase, accumulation of crosslinked proteins, and loss of erythrocyte deformability.