Vanadate-Induced Suicidal Erythrocyte Death

Vanadium, a trace element, as vanadate (VO₄^3–) is known to interfere with a wide variety of enzymes including Ca²⁺ ATPase and Na⁺/K⁺ ATPase. VO₄^3– is excreted mainly via the kidney. In renal insufficiency, the impaired VO₄^3– excretion leads to VO₄^3– accumulation in blood.The present study explored the effect of VO₄^3– on eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptotic cells are phagocytosed and thus rapidly cleared from circulating blood. Stimulators of eryptosis include an increase of the cytosolic Ca²⁺ concentration. Erythrocyte Ca²⁺ activity was estimated from Fluo-3 fluorescence, phosphatidylserine exposure from annexin V-binding, and erythrocyte volume from forward scatter in FACS analysis. Exposure of erythrocytes to VO₄^3– increased cytosolic Ca²⁺ concentration, enhanced the percentage of annexin V-binding erythrocytes, decreased erythrocyte forward scatter, and lowered the intracellular ATP concentration. In conclusion, VO₄^3– induces eryptosis at least partially through increase of cytosolic Ca²⁺ concentration, an effect presumably contributing to the development of anemia in chronic renal failure.