Eryptosis, a Window to Systemic Disease

Abstract

Similar to apoptosis of nucleated cells, suicidal erythrocyte death or eryptosis is characterized by cell shrinkage, membrane blebbing and membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Signaling of eryptosis involves formation of prostaglandin E₂ with subsequent activation of cation channels and Ca²⁺-entry and/or release of platelet activating factor (PAF) with subsequent activation of sphingomyelinase and formation of ceramide. Ca²⁺ and ceramide stimulate cell membrane scrambling. Ca²⁺ further activates Ca²⁺-sensitive K⁺-channels leading to cellular KCl loss and cell shrinkage and stimulates the protease calpain resulting in degradation of the cytoskeleton. Injuries triggering eryptosis may similarly compromise survival of nucleated cells. The case is made that analysis of enhanced eryptosis may direct to the pathophysiology of systemic disease. Examples presented include drug side effects, sepsis, haemolytic uremic syndrome, Wilson´s disease, phosphate depletion and a rare condition caused by a mutation in GLUT1 turning the carrier into a cation channel.

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

“…Erythrocytes are very sensitive to ROS due to the high poly-unsaturated fatty acids (PUFAs) content in the membrane [25]. The pool of ROS can induce oxidative stress and eventually trigger apoptosis that impairs the function of erythrocytes [24,26] and leads to a wide variety of further diseases or clinical conditions [27]. Thus, it is important to protect erythrocytes against oxidative stress and apoptosis.…”

Hemin-induced suicidal erythrocyte death

“…Hemin-induced damage of erythrocytes is considered to be largely due to hemolysis [48,49,59,70]. However, several conditions leading to hemolysis have recently been shown to trigger eryptosis, the suicidal death of erythrocytes [40]. Hallmarks of eryptosis are scrambling of the erythrocyte membrane and cell shrinkage [40].…”

“…However, several conditions leading to hemolysis have recently been shown to trigger eryptosis, the suicidal death of erythrocytes [40]. Hallmarks of eryptosis are scrambling of the erythrocyte membrane and cell shrinkage [40]. The cell membrane scrambling leads to exposure of phosphatidylserine at their surface, which is apparent from annexin V-binding of the erythrocytes [40].…”

“…Hallmarks of eryptosis are scrambling of the erythrocyte membrane and cell shrinkage [40]. The cell membrane scrambling leads to exposure of phosphatidylserine at their surface, which is apparent from annexin V-binding of the erythrocytes [40]. Cell shrinkage is apparent from a decrease of forward scatter in fluorescence-activated cell sorter (FACS) analysis [40].…”

“…The cell membrane scrambling leads to exposure of phosphatidylserine at their surface, which is apparent from annexin V-binding of the erythrocytes [40]. Cell shrinkage is apparent from a decrease of forward scatter in fluorescence-activated cell sorter (FACS) analysis [40]. Eryptosis is stimulated by increase in cytosolic Ca 2+ activity [5,11,12,19,41].…”