Related Experiment Video
Updated: May 17, 2026
Induction of Eryptosis in Red Blood Cells Using a Calcium Ionophore
Published on: January 21, 2020
Stimulation of suicidal erythrocyte death by fumagillin
Mohanad Zbidah1, Adrian Lupescu, Kashif Jilani
1Department of Physiology, University of Tuebingen, Tuebingen, Germany.
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.
Insights
Fumagillin, an antifungal compound, triggers eryptosis, the suicidal death of red blood cells. This process involves increased calcium, ceramide, and phosphatidylserine exposure, indicating a new mechanism for fumagillin
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Fumagillin, derived from Aspergillus fumigatus, exhibits anti-infective and anti-cancer properties.
- Apoptosis, or programmed cell death, is a known mechanism for fumagillin's effects.
- Eryptosis, the suicidal death of erythrocytes, shares similarities with apoptosis and is triggered by increased intracellular calcium and ceramide.
Purpose of the Study:
- To investigate whether fumagillin stimulates eryptosis in erythrocytes.
- To elucidate the specific mechanisms by which fumagillin might induce eryptosis.
Main Methods:
- Erythrocytes were exposed to varying concentrations of fumagillin (5-100 μM) for 48 hours.
- Intracellular calcium levels ([Ca(2+)](i)) were measured using Fluo3 fluorescence.
- Ceramide levels, phosphatidylserine exposure (annexin V binding), cell volume (forward scatter), and hemoglobin release (hemolysis) were quantified.
Main Results:
- Fumagillin exposure significantly increased intracellular calcium, ceramide abundance, and phosphatidylserine exposure.
- A decrease in erythrocyte cell volume and a slight increase in hemolysis were observed.
- Removal of extracellular calcium partially inhibited fumagillin-induced phosphatidylserine exposure.
Conclusions:
- Fumagillin stimulates eryptosis, characterized by increased intracellular calcium and ceramide.
- The study reveals a novel mechanism of fumagillin action involving eryptosis induction.
- Fumagillin's effects on erythrocytes are linked to calcium influx, ceramide formation, and cell volume reduction.
Related Concept Videos
01:25Inhibitors of Bacterial Protein Synthesis
01:15Antifungal Agents