Stimulation of Erythrocyte Cell Membrane Scrambling by Gedunin

Cellular Physiology and Biochemistry

关键词: Phosphatidylserine;    Gedunin;    Calcium;    Malaria;    Anemia;    Cell volume;    Eryptosis;   

DOI  :  10.1159/000362962

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/Aims Gedunin, an inhibitor of heat shock protein HSP90, triggers apoptosis of tumor cells and is thus effective against malignancy. Moreover, the drug has antimalarial potency. In analogy to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i). The present study explored whether gedunin stimulates eryptosis. Methods Forward scatter was determined to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to depict hemolysis, and Fluo3-fluorescence to quantify [Ca²⁺]_i. Results A 48 h exposure of human erythrocytes to gedunin significantly increased [Ca²⁺]_i (12 µM), significantly decreased forward scatter (24 µM) and significantly increased annexin-V-binding (12 µM). The effect of gedunin (24 µM) on annexin-V-binding was virtually abrogated by removal of extracellular Ca²⁺. Conclusion Gedunin stimulates suicidal erythrocyte death or eryptosis, an effect mainly if not exclusively due to stimulation of Ca²⁺ entry.

【 授权许可】

CC BY-NC-ND