Induction of Suicidal Erythrocyte Death by Novobiocin

Cellular Physiology and Biochemistry

关键词: Phosphatidylserine;    Calcium;    Cell volume;    Eryptosis;   

DOI  :  10.1159/000358643

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background Novobiocin, an aminocoumarin antibiotic, interferes with heat shock protein 90 and hypoxia inducible factor dependent gene expression and thus compromises cell survival. Similar to survival of nucleated cells, erythrocyte survival could be disrupted by eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and by phospholipd scrambling of the cell membrane with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i). The Ca²⁺ sensitivity of phospholipid scrambling is enhanced by ceramide. The present study explored, whether novobiocin elicits eryptosis. Methods [Ca²⁺]_i was estimated from Fluo3-fluorescence, ceramide abundance utilizing fluorescent antibodies, cell volume from forward scatter, phosphatidylserine-exposure from annexin V binding. Results A 48 hours exposure to novobiocin (500 µM) was followed by a significant increase of [Ca²⁺]_i, decrease of forward scatter, increase of annexin-V-binding and enhanced ceramide formation. Removal of extracellular Ca²⁺ virtually abrogated the increase of annexin-V-binding following novobiocin exposure. Conclusions Novobiocin stimulates eryptosis, an effect at least in part due to entry of extracellular Ca²⁺ and formation of ceramide.

【 授权许可】

CC BY-NC-ND