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Mitoxantrone-Induced Suicidal Erythrocyte Death.
MedLine Citation:
PMID:  25427644     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background/Aims: Mitoxantrone, a cytotoxic drug used for the treatment of malignancy and multiple sclerosis, is at least in part effective by triggering apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a type of suicidal cell death. Hallmarks of eryptosis are cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signalling involved in eryptosis include Ca(2+)-entry, ceramide formation and oxidative stress. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, formation of reactive oxidant species (ROS) from 2',7'-dichlorodihydrofluorescein-diacetate fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 hours exposure to mitoxantrone was followed by significant decrease of forward scatter (≥ 5 μg/ml mitoxantrone) and increase of annexin-V-binding (≥ 10 μg/ml mitoxantrone), effects paralleled by significant increases of ROS formation (25 μg/ml mitoxantrone) and ceramide abundance (25 μg/ml mitoxantrone). The effect of mitoxantrone was not significantly modified by nominal absence of extracellular Ca(2+) but significantly blunted by the antioxidant N-acetylcysteine (1 mM). Conclusions: Mitoxantrone triggers cell membrane scrambling, an effect not requiring entry of extracellular Ca(2+) but at least partially due to formation of ROS and ceramide. © 2014 S. Karger AG, Basel.
Authors:
Markus Arnold; Rosi Bissinger; Florian Lang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-12
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  34     ISSN:  1421-9778     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-27     Completed Date:  -     Revised Date:  2014-11-28    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1756-1767     Citation Subset:  -    
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