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Stimulation of suicidal erythrocyte death by fumagillin.
- Source :
-
Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2013 May; Vol. 112 (5), pp. 346-51. Date of Electronic Publication: 2012 Dec 06. - Publication Year :
- 2013
-
Abstract
- Fumagillin, a cyclohexane isolated from fungus Aspergillus fumigatus, has anti-infective and anti-cancer potency. Fumagillin is at least partially effective by inducing suicidal death or apoptosis. In analogy to apoptosis of nucleated cells, eryptosis is the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)](i)) and ceramide. The present study explored whether fumagillin (5-100 μM) could stimulate eryptosis. To this end, [Ca(2+)](i) was estimated from Fluo3 fluorescence, ceramide by utilizing specific antibodies, cell volume from forward scatter, phosphatidylserine exposure from annexin V binding and haemolysis from haemoglobin release. As a result, a 48-hr exposure to fumagillin significantly increased [Ca(2+)](i) (≥10 μM), enhanced ceramide abundance (100 μM), triggered annexin V binding (≥10 μM) and decreased forward scatter (≥10 μM). Fumagillin exposure was followed by slight but significant increase of haemolysis. Removal of extracellular Ca(2+) significantly blunted but did not abolish the effect of fumagillin (100 μM) on annexin V binding. The present observations disclose a novel effect of fumagillin, that is, stimulation of eryptosis, paralleled by Ca(2+) entry, ceramide formation, phosphatidylserine exposure and decrease of cell volume.<br /> (© 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.)
- Subjects :
- Annexin A5 metabolism
Calcium metabolism
Cell Death drug effects
Cell Size drug effects
Ceramides metabolism
Dose-Response Relationship, Drug
Erythrocytes metabolism
Erythrocytes pathology
Flow Cytometry methods
Hemolysis drug effects
Humans
Phosphatidylserines metabolism
Protein Binding
Sesquiterpenes toxicity
Anti-Bacterial Agents toxicity
Cyclohexanes toxicity
Erythrocytes drug effects
Fatty Acids, Unsaturated toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1742-7843
- Volume :
- 112
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Basic & clinical pharmacology & toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 23121865
- Full Text :
- https://doi.org/10.1111/bcpt.12033