Enhanced susceptibility to erythrocyte ?apoptosis? following phosphate depletion

Abstract

Among the sequelae of phosphate depletion is anaemia, due in part to a decreased life span of mature erythrocytes. Recent studies have disclosed that cellular stress leads to an increase of cytosolic Ca(2+) activity in erythrocytes thereby triggering cell shrinkage and breakdown of phosphatidylserine asymmetry of the cell membrane, both typical features of apoptosis. In the present experiments, phosphatidylserine exposure and cell size were measured by fluorescence-activated cell sorting (FACS) analysis of annexin binding and forward scatter, respectively. Erythrocytes from intact mice were compared with erythrocytes from mice exposed to a low-phosphate diet for 4 days. Annexin binding of freshly drawn erythrocytes was slightly but significantly enhanced by the low-phosphate diet. Furthermore, intracellular phosphate and ATP concentrations were significantly decreased in those erythrocytes whereas intracellular Ca(2+) activity was unaltered. Osmotic shock (exposure to 700 mOsm by addition of sucrose for 12 h), removal of Cl(-) (replaced by gluconate for 15 h) or removal of glucose (12 h) decreased cell volume and increased the number of annexin-binding erythrocytes. Interestingly, these effects were significantly larger in erythrocytes from phosphate-depleted animals. The experiments reveal a novel mechanism triggered by phosphate depletion that presumably contributes to the enhanced vulnerability and accelerated sequestration of erythrocytes and, thus, to anaemia.

Hemin-induced suicidal erythrocyte death

“…A wide variety of clinical disorders is known to stimulate eryptosis, including iron deficiency [36], phosphate depletion [6], hemolytic uremic syndrome [43], sepsis [35], malaria [10,37,38], or Wilson's disease [46]. Some of these diseases may cause eryptosis by stimulating the formation of hemin.…”

Erythrocyte programmed cell death

“…Eryptosis has been observed in a wide variety of clinical conditions, including sepsis (135), hemolytic uremic syndrome (136), renal insuficiency (98), malaria infection (123), sicklecell anemia (137), b-thalassemia (40), glucose-6-phosphate dehydrogenase (G6PD)-deficiency (40), phosphate depletion (138) and Wilsons disease (67).…”

Influence of feeding a low-phosphorus diet on leucocyte function in dairy cows

“…High intracellular [Ca] interfere with mitochondrial oxidation and ATP synthesis and impair Ca signaling in the cell (Alexiewicz et al, 1991;Massry and Fadda, 1993) and, therefore, lead to a reversible loss of cell function in different cell types Zhou et al, 1991;Kiersztejn et al, 1992;Massry and Fadda, 1993). In addition, human and mouse erythrocytes have been shown to undergo rapid self-destruction and disintegration due to Ca influx (Bratosin et al, 2001;Birka et al, 2004). Similarly intra-and extracellular [Ca] have been described to be important for cell function of smooth muscle cells and PMNL in dairy cows (Jørgensen et al, 1998;Martinez et al, 2014).…”