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Stimulation of Suicidal Erythrocyte Death by Ellipticine
Author(s) -
Calabrò Salvatrice,
Alzoubi Kousi,
Bissinger Rosi,
Faggio Caterina,
Lang Florian
Publication year - 2015
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12350
Subject(s) - phosphatidylserine , ceramide , oxidative stress , apoptosis , chemistry , annexin , programmed cell death , reactive oxygen species , cytosol , mitochondrion , annexin a5 , microbiology and biotechnology , biochemistry , biology , membrane , phospholipid , enzyme
Ellipticine is a potent antineoplastic alkaloid effective in part by triggering apoptosis. Mechanisms involved in ellipticine‐induced apoptosis include mitochondrial depolarization and DNA damage. Erythrocytes lack mitochondria and nuclei but may nevertheless enter suicidal death or eryptosis, which is characterized by cell shrinkage and phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase in cytosolic Ca 2+ activity ([Ca 2+ ] i ), ceramide formation and oxidative stress. This study tested whether ellipticine stimulates eryptosis. Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter (FSC), [Ca 2+ ] i from Fluo‐3 fluorescence, ceramide abundance from binding of specific antibodies and reactive oxygen species from 2′,7′‐dichlorodihydrofluorescein diacetate fluorescence. A 24‐hr exposure of human erythrocytes to ellipticine (5 μg/ml) significantly increased the percentage of annexin V binding cells, ceramide abundance and oxidative stress. Ellipticine did not significantly modify [Ca 2+ ] i , and the stimulation of annexin V binding by ellipticine (5 μg/ml) did not require the presence of extracellular Ca 2+ . Ellipticine (5 μg/ml) did not significantly modify FSC. Ionomycin (1 μM, 1 hr) decreased FSC, an effect slightly but significantly blunted by ellipticine (5 μg/ml). Ellipticine thus stimulates phosphatidylserine translocation in the erythrocyte cell membrane, an effect at least partially due to stimulation of oxidative stress and ceramide formation.