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Induction of Eryptosis in Red Blood Cells Using a Calcium Ionophore
Published on: January 21, 2020
Gossypol-induced suicidal erythrocyte death
Mohanad Zbidah1, Adrian Lupescu, Nazneen Shaik
1Department of Physiology, University of Tuebingen, Gmelinstrasse 5, 72076 Tuebingen, Germany.
Toxicology
|October 9, 2012
Summary
Gossypol, a compound found in cotton plants, triggers suicidal erythrocyte death (eryptosis), leading to anemia. This study reveals gossypol
Area of Science:
- Hematology
- Toxicology
- Cell Biology
Background:
- Gossypol, a polyphenolic compound from Gossypium species, exhibits male contraceptive, anticancer, antimicrobial, and antiviral properties.
- A known side effect of gossypol is anemia, linked to accelerated erythrocyte demise.
- Eryptosis, or suicidal erythrocyte death, is characterized by cell shrinkage and phosphatidylserine exposure, leading to erythrocyte clearance.
Purpose of the Study:
- To investigate whether gossypol stimulates eryptosis in human erythrocytes.
- To elucidate the mechanism by which gossypol induces erythrocyte death.
Main Methods:
- Flow cytometry was employed to assess cytosolic Ca(2+) activity ([Ca(2+)](i)) using Fluo-3 fluorescence.
- Cell volume was measured by forward scatter, and phosphatidylserine exposure was quantified by annexin-V binding.
- Hemolysis was determined by hemoglobin release, and the role of extracellular Ca(2+) was examined.
Main Results:
- Exposure to 0.75 μM gossypol for 48 hours significantly increased [Ca(2+)](i), decreased cell volume (forward scatter), and elevated annexin-V binding.
- Gossypol exposure resulted in a slight but significant increase in hemolysis.
- The absence of extracellular Ca(2+) significantly reduced the effect of 1 μM gossypol on annexin-V binding, indicating a Ca(2+)-dependent mechanism.
Conclusions:
- Gossypol induces eryptosis in human erythrocytes through a Ca(2+)-dependent mechanism.
- This gossypol-induced eryptosis contributes to or fully explains the anemia associated with gossypol treatment.
- The findings reveal a novel mechanism for gossypol's adverse effects on erythrocytes.
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