期刊
TOXICOLOGY IN VITRO
卷 27, 期 1, 页码 52-58出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2012.09.004
关键词
Phosphatidylserine; Withaferin A; Calcium; Cell volume; Eryptosis
类别
资金
- Deutsche Forschungsgemeinschaft
Withaferin A, a triterpenoid component from Withania somnifera, counteracts malignancy, an effect attributed to stimulation of apoptosis. Withaferin A is partially effective through induction of oxidative stress, altered gene expression and mitochondria! depolarization. Erythrocytes lack mitochondria and nuclei but may enter apoptosis-like eiyptosis, a suicidal cell death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca2+-activity [Ca2+](i) following activation of oxidant-sensitive Ca2+-permeable cation channels, ceramide formation and/or ATP-depletion. The present study explored, whether withaferin A triggers eryptosis. To this end, [Ca2+](i) was estimated from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin-V-binding, hemolysis from hemoglobin release, oxidative stress from DCFDA-fluorescence and ceramide abundance utilizing antibodies. A 48 h exposure to withaferin A significantly decreased forward scatter (at >= 10 mu M withaferin concentration) and increased [Ca2+](i) (>= 5 mu M), ROS-formation (>= 10 mu M) ceramide-formation (>= 10 mu M) as well as annexin-V-binding (>= 5 mu M). Withaferin A treatment was followed by slight but significant increase of hemolysis. Extracellular Ca2+ removal, amiloride, and the antioxidant N-acetyl-L-cysteine significantly blunted withaferin A-triggered annexin-V-binding. The present observations reveal that withaferin A triggers suicidal erythrocyte death despite the absence of gene expression and key elements of apoptosis such as mitochondria. (c) 2012 Elsevier Ltd. All rights reserved.
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